Jungfraujoch/rugnux/ModelValidation.cpp

// SPDX-FileCopyrightText: 2026 Filip Leonarski, Paul Scherrer Institute <filip.leonarski@psi.ch>
// SPDX-License-Identifier: GPL-3.0-only

#include "ModelValidation.h"

#include <algorithm>
#include <cmath>
#include <complex>
#include <array>
#include <string>
#include <vector>
#include <unordered_map>

#include <gemmi/pdb.hpp>       // read_pdb
#include <gemmi/gz.hpp>        // MaybeGzipped
#include <gemmi/it92.hpp>      // IT92 x-ray form factors
#include <gemmi/dencalc.hpp>   // DensityCalculator
#include <gemmi/fourier.hpp>   // transform_map_to_f_phi, get_f_phi_on_grid, transform_f_phi_grid_to_map
#include <gemmi/solmask.hpp>   // SolventMasker
#include <gemmi/scaling.hpp>   // Scaling (bulk solvent + anisotropic B)
#include <gemmi/ccp4.hpp>      // Ccp4 map I/O
#include <gemmi/mtz.hpp>       // Mtz (map-coefficient output)

#include "../common/Logger.h"
#include "../image_analysis/scale_merge/ReindexAmbiguity.h"   // ReindexReflections

namespace {

using Table = gemmi::IT92<float>;

// Stable key for a Miller index reduced into the ASU (indices are small, well within +/-512).
long hkl_key(const gemmi::Miller &h) {
    return (h[0] + 512L) * 1048576 + (h[1] + 512L) * 1024 + (h[2] + 512L);
}

// Write an FFT of ASU map coefficients as a CCP4 map; return its RMS (for reporting / sigma units).
double write_ccp4(gemmi::AsuData<std::complex<float>> &coef, const std::string &path) {
    coef.ensure_sorted();
    std::array<int, 3> size = gemmi::get_size_for_hkl(coef, {{0, 0, 0}}, 3.0);
    gemmi::Grid<float> map =
        gemmi::transform_f_phi_grid_to_map(gemmi::get_f_phi_on_grid<float>(coef, size, true));
    gemmi::Ccp4<float> ccp4;
    ccp4.grid = map;
    ccp4.update_ccp4_header(2);
    ccp4.write_ccp4_map(path);
    return ccp4.hstats.rms;
}

}  // namespace

ModelValidationResult ValidateAgainstModel(const std::vector<MergedReflection> &merged,
                                           const UnitCell &cell,
                                           const std::string &model_path,
                                           const std::string &output_prefix,
                                           Logger &logger,
                                           std::optional<int> data_space_group_number,
                                           bool probe_indexing_ambiguity) {
    ModelValidationResult result;

    // --- read the atomic model ---
    gemmi::Structure st;
    try {
        st = gemmi::read_pdb(gemmi::MaybeGzipped(model_path));
    } catch (const std::exception &e) {
        logger.Error("Model validation: cannot read model {}: {}", model_path, e.what());
        return result;
    }
    if (st.models.empty() || !st.cell.is_crystal()) {
        logger.Error("Model validation: model {} has no atoms or no unit cell", model_path);
        return result;
    }
    const gemmi::SpaceGroup *sg = st.find_spacegroup();
    if (!sg) {
        logger.Error("Model validation: model {} has no usable space group", model_path);
        return result;
    }
    result.model_space_group_number = sg->number;

    // If the data was indexed in the enantiomorph of the model's space group (e.g. data P4(1)2(1)2,
    // model P4(3)2(1)2 - the merged intensities cannot tell them apart), reindex the observed
    // reflections into the model's hand so the two settings agree. This does not change the
    // R-factors (which use |F|), but keeps the observed data consistent with the model.
    std::vector<MergedReflection> reindexed;
    const std::vector<MergedReflection> *obs_ptr = &merged;
    if (data_space_group_number && *data_space_group_number != sg->number) {
        const gemmi::SpaceGroup *dsg = gemmi::find_spacegroup_by_number(*data_space_group_number);
        if (dsg && dsg->is_enantiomorphic() && sg->is_enantiomorphic()) {
            gemmi::GroupOps eops = dsg->operations();
            eops.change_basis_forward(dsg->change_of_hand_op());
            const gemmi::SpaceGroup *enant = gemmi::find_spacegroup_by_ops(eops);
            if (enant && enant->number == sg->number) {
                reindexed = ReindexReflections(merged, dsg->change_of_hand_op());
                obs_ptr = &reindexed;
                result.hand_op = dsg->change_of_hand_op();
                logger.Info("Model validation: data space group {} is the enantiomorph of the model {}; "
                            "reindexed the observed reflections into the model's hand",
                            dsg->short_name(), sg->hm);
            }
        }
    }
    const std::vector<MergedReflection> &obs = *obs_ptr;

    // Resolution limit from the data (the merged set is already resolution-trimmed).
    double d_min = 0.0;
    for (const MergedReflection &r : obs)
        if (r.d > 0 && (d_min == 0.0 || r.d < d_min))
            d_min = r.d;
    if (d_min <= 0.0) {
        logger.Error("Model validation: merged reflections carry no resolution");
        return result;
    }

    // Re-fractionalize the model into the data cell (rigid cell adjustment; no refinement).
    const gemmi::UnitCell data_cell = cell;  // UnitCell -> gemmi::UnitCell
    if (data_cell.is_crystal()) {
        gemmi::UnitCell old = st.cell;
        for (gemmi::Model &m : st.models)
            for (gemmi::Chain &ch : m.chains)
                for (gemmi::Residue &r : ch.residues)
                    for (gemmi::Atom &a : r.atoms)
                        a.pos = data_cell.orthogonalize(old.fractionalize(a.pos));
        st.cell = data_cell;
    }
    st.setup_cell_images();
    const gemmi::UnitCell &ucell = st.cell;

    logger.Info("Model validation: {} atoms, cell a={:.2f} b={:.2f} c={:.2f}, sg {}, to {:.2f} A",
                gemmi::count_atom_sites(st.models[0]), ucell.a, ucell.b, ucell.c, sg->hm, d_min);

    // --- Fcalc (atomic) via electron density on a grid + FFT ---
    gemmi::DensityCalculator<Table, float> dc;
    dc.d_min = d_min;
    dc.rate = 1.5;
    dc.set_grid_cell_and_spacegroup(st);
    dc.set_refmac_compatible_blur(st.models[0]);
    dc.put_model_density_on_grid(st.models[0]);
    gemmi::AsuData<std::complex<float>> fcalc =
        gemmi::transform_map_to_f_phi(dc.grid, true).prepare_asu_data(dc.d_min, dc.blur, false, false, false);

    // --- flat bulk-solvent mask -> Fmask ---
    // Refmac radii give a slightly lower R than the Cctbx set on our test cases, at no cost.
    gemmi::SolventMasker masker(gemmi::AtomicRadiiSet::Refmac);
    gemmi::Grid<float> mask_grid;
    mask_grid.unit_cell = dc.grid.unit_cell;
    mask_grid.spacegroup = dc.grid.spacegroup;
    mask_grid.set_size_from_spacing(dc.requested_grid_spacing(), gemmi::GridSizeRounding::Up);
    masker.put_mask_on_grid(mask_grid, st.models[0]);
    gemmi::AsuData<std::complex<float>> fmask =
        gemmi::transform_map_to_f_phi(mask_grid, true).prepare_asu_data(dc.d_min, 0);

    gemmi::GroupOps gops = sg->operations();
    gemmi::ReciprocalAsu asu(sg);

    // --- fit the (scaled, solvent-corrected) model to one observed set and score it ---
    // Factored into a lambda so we can probe indexing (merohedral) ambiguities: run the same scale +
    // R computation on each reindexing of the observed reflections and keep the lowest-R-free one.
    struct Fit {
        gemmi::AsuData<std::complex<float>> fmodel, map2fofc, mapfofc;
        std::unordered_map<long, std::pair<double, bool>> obs_by_hkl;  // hkl -> (Fobs, is_free)
        double r_work = 1, r_free = 1, k_sol = 0, b_sol = 0, k_overall = 0;
        int n_w = 0, n_f = 0;
    };
    auto fit_model = [&](const std::vector<MergedReflection> &obs_in) -> Fit {
        Fit out;
        out.fmodel = fcalc;   // copy the atomic structure factors; scaling mutates them in place

        // --- observed amplitudes into the model ASU, keyed by hkl (also remember free flag) ---
        // Observed amplitudes are the French-Wilson |F| already computed at the end of the merge
        // (MergedReflection.F), so the model R-free / maps use exactly the same amplitudes as the
        // written reflection file.
        gemmi::AsuData<gemmi::ValueSigma<float>> fobs;
        fobs.unit_cell_ = ucell;
        fobs.spacegroup_ = sg;
        for (const MergedReflection &r : obs_in) {
            if (std::isnan(r.F)) continue;
            gemmi::Miller h{{r.h, r.k, r.l}};
            if (!asu.is_in(h)) h = asu.to_asu(h, gops).first;
            fobs.v.push_back({h, {r.F, 1.0f}});
            out.obs_by_hkl[hkl_key(h)] = {r.F, r.rfree_flag};
        }
        fobs.ensure_asu();
        fobs.ensure_sorted();

        // --- scale Fmodel(+solvent) to Fobs: k_overall, anisotropic B, k_sol, b_sol ---
        gemmi::Scaling<float> scaling(ucell, sg);
        scaling.use_solvent = true;
        scaling.prepare_points(out.fmodel, fobs, &fmask);
        scaling.fit_isotropic_b_approximately();
        scaling.fit_parameters();
        scaling.scale_data(out.fmodel, &fmask);   // out.fmodel now holds the scaled, solvent-corrected Fmodel
        out.k_sol = scaling.k_sol;
        out.b_sol = scaling.b_sol;
        out.k_overall = scaling.k_overall;

        // The model is scaled to the data with an overall scale, an anisotropic B and a flat bulk
        // solvent only - the standard, few-parameter model that refinement programs use. A dataset-
        // specific free-form per-resolution-shell rescale would lower this dataset's R a little, but
        // it reshapes each map's radial amplitude profile differently, so a batch of maps would no
        // longer be directly comparable. For a fragment-screening / PanDDA campaign, comparable maps
        // across datasets matter more than the last bit of per-dataset R, so it is deliberately omitted.

        // --- R-work / R-free and map coefficients (2Fo-Fc and Fo-Fc, model phases) ---
        out.map2fofc.unit_cell_ = ucell; out.map2fofc.spacegroup_ = sg;
        out.mapfofc.unit_cell_ = ucell;  out.mapfofc.spacegroup_ = sg;
        double num_w = 0, den_w = 0, num_f = 0, den_f = 0;
        for (const auto &hv : out.fmodel.v) {
            auto it = out.obs_by_hkl.find(hkl_key(hv.hkl));
            if (it == out.obs_by_hkl.end()) continue;
            double Fo = it->second.first;
            double Fc = std::abs(hv.value);
            double phi = std::arg(hv.value);
            if (it->second.second) { num_f += std::fabs(Fo - Fc); den_f += Fo; ++out.n_f; }
            else                   { num_w += std::fabs(Fo - Fc); den_w += Fo; ++out.n_w; }
            std::complex<float> ph = std::polar(1.0f, static_cast<float>(phi));
            out.map2fofc.v.push_back({hv.hkl, static_cast<float>(2 * Fo - Fc) * ph});
            out.mapfofc.v.push_back({hv.hkl, static_cast<float>(Fo - Fc) * ph});
        }
        out.r_work = den_w > 0 ? num_w / den_w : 1;
        out.r_free = den_f > 0 ? num_f / den_f : 1;
        return out;
    };

    // --- indexing (merohedral) ambiguity ---
    // When a reference MTZ was supplied, the data were already reindexed to agree with the reference
    // intensities (at the merge stage for rotation data, per image in stills scaling), and that
    // choice is authoritative - we keep it. Only with a model and NO reference do we resolve the
    // ambiguity here, as a fallback, by fitting each candidate reindexing and keeping the lowest
    // R-free. A no-op either way for a holohedral crystal (no twin laws). The
    // enantiomorph/screw ambiguity is never probed by R-free: |Fcalc| is the same for both hands, so
    // it cannot distinguish them - that is taken from the model hand above.
    Fit best = fit_model(obs);
    if (probe_indexing_ambiguity) {
        const auto reindex_ops = ReindexAmbiguityOperators(cell, sg->number);
        std::vector<double> candidate_r_free{best.r_free};   // identity first, then the twin laws
        for (const auto &op : reindex_ops) {
            Fit cand = fit_model(ReindexReflections(obs, op));
            candidate_r_free.push_back(cand.r_free);
            if (cand.r_free < best.r_free) { best = std::move(cand); result.indexing_op = op; }
        }
        if (!reindex_ops.empty()) {
            // The runner-up as well as the winner: the margin between them is what says whether the
            // choice was made on evidence, and on weak data the two can come out within noise.
            std::sort(candidate_r_free.begin(), candidate_r_free.end());
            logger.Info("Model validation: no reference - probed {} indexing solution(s) against the model; "
                        "{} (R-free {:.4f}, runner-up {:.4f})", candidate_r_free.size(),
                        result.indexing_op == gemmi::Op::identity() ? "kept the current indexing"
                                                                    : "reindexed to the lower-R-free solution",
                        candidate_r_free[0], candidate_r_free[1]);
        }
    }

    gemmi::AsuData<std::complex<float>> &fmodel = best.fmodel;
    gemmi::AsuData<std::complex<float>> &map2fofc = best.map2fofc;
    gemmi::AsuData<std::complex<float>> &mapfofc = best.mapfofc;
    std::unordered_map<long, std::pair<double, bool>> &obs_by_hkl = best.obs_by_hkl;

    result.r_work = best.r_work;
    result.r_free = best.r_free;
    result.n_work = best.n_w;
    result.n_free = best.n_f;
    result.k_sol = best.k_sol;
    result.b_sol = best.b_sol;
    result.k_overall = best.k_overall;

    // --- write the maps and score the 2Fo-Fc map at atom centres (a real map peaks there) ---
    const std::string p2 = output_prefix + "_2fofc.ccp4";
    const std::string pd = output_prefix + "_fofc.ccp4";
    double rms2 = write_ccp4(map2fofc, p2);
    write_ccp4(mapfofc, pd);

    // Recompute the 2Fo-Fc real-space grid once more to sample it at atom positions.
    {
        map2fofc.ensure_sorted();
        std::array<int, 3> size = gemmi::get_size_for_hkl(map2fofc, {{0, 0, 0}}, 3.0);
        gemmi::Grid<float> grid =
            gemmi::transform_f_phi_grid_to_map(gemmi::get_f_phi_on_grid<float>(map2fofc, size, true));
        double s = 0; int n = 0;
        for (gemmi::Model &m : st.models)
            for (gemmi::Chain &ch : m.chains)
                for (gemmi::Residue &r : ch.residues)
                    for (gemmi::Atom &a : r.atoms) { s += grid.interpolate_value(a.pos); ++n; }
        result.mean_atom_density_sigma = (n > 0 && rms2 > 0) ? (s / n) / rms2 : 0;
    }

    // --- MTZ of map coefficients so the maps can be re-opened / rebuilt in Coot etc. ---
    try {
        gemmi::Mtz mtz(true);
        mtz.spacegroup = sg;
        mtz.set_cell_for_all(ucell);
        mtz.add_dataset("model_validation");
        mtz.add_column("FP", 'F', -1, -1, false);
        mtz.add_column("FC", 'F', -1, -1, false);
        mtz.add_column("PHIC", 'P', -1, -1, false);
        mtz.add_column("FWT", 'F', -1, -1, false);
        mtz.add_column("PHWT", 'P', -1, -1, false);
        mtz.add_column("DELFWT", 'F', -1, -1, false);
        mtz.add_column("PHDELWT", 'P', -1, -1, false);
        mtz.add_column("FREE", 'I', -1, -1, false);
        std::vector<float> data;
        int nref = 0;
        for (const auto &hv : fmodel.v) {
            auto it = obs_by_hkl.find(hkl_key(hv.hkl));
            if (it == obs_by_hkl.end()) continue;
            double Fo = it->second.first;
            double Fc = std::abs(hv.value);
            double phi_deg = gemmi::phase_in_angles(hv.value);
            data.insert(data.end(), {static_cast<float>(hv.hkl[0]), static_cast<float>(hv.hkl[1]),
                                     static_cast<float>(hv.hkl[2]),
                                     static_cast<float>(Fo), static_cast<float>(Fc),
                                     static_cast<float>(phi_deg),
                                     static_cast<float>(2 * Fo - Fc), static_cast<float>(phi_deg),
                                     static_cast<float>(Fo - Fc), static_cast<float>(phi_deg),
                                     it->second.second ? 0.0f : 1.0f});
            ++nref;
        }
        mtz.nreflections = nref;
        mtz.data = std::move(data);
        mtz.write_to_file(output_prefix + "_maps.mtz");
    } catch (const std::exception &e) {
        logger.Warning("Model validation: could not write map MTZ: {}", e.what());
    }

    result.ok = true;
    result.maps_prefix = output_prefix;
    logger.Info("Model validation: R-work={:.4f} ({} refl)  R-free={:.4f} ({} refl)  "
                "[overall + anisotropic B + bulk solvent]",
                result.r_work, result.n_work, result.r_free, result.n_free);
    logger.Info("Model validation: bulk solvent k_sol={:.3f} b_sol={:.1f}, k_overall={:.3f}",
                result.k_sol, result.b_sol, result.k_overall);
    logger.Info("Model validation: mean 2Fo-Fc density at atom centres = {:.2f} sigma", result.mean_atom_density_sigma);
    logger.Info("Model validation: wrote {}_2fofc.ccp4, {}_fofc.ccp4, {}_maps.mtz",
                output_prefix, output_prefix, output_prefix);
    return result;
}

namespace {

// The reindexing operator as it reads on Miller indices ("k,h,-l" rather than "y,x,-z").
std::string hkl_triplet(const gemmi::Op &op) {
    std::string t = op.triplet();
    std::replace(t.begin(), t.end(), 'x', 'h');
    std::replace(t.begin(), t.end(), 'y', 'k');
    std::replace(t.begin(), t.end(), 'z', 'l');
    return t;
}

}  // namespace

int AdoptModelFrame(const ModelValidationResult &validation,
                    std::vector<MergedReflection> &merged,
                    int data_space_group_number,
                    bool merge_friedel,
                    Logger &logger) {
    int space_group_number = data_space_group_number;
    if (!validation.ok)
        return space_group_number;

    // The change of hand also changes the space group the reflections are in: P4(1)2(1)2 data written
    // in the model's hand are P4(3)2(1)2 data. The merged intensities are the same measurements either
    // way - the enantiomorph is exactly what they cannot distinguish - so the model's hand is the only
    // evidence there is, and adopting it is what makes the file refinable against that model.
    if (!(validation.hand_op == gemmi::Op::identity()) && validation.model_space_group_number > 0) {
        merged = ReindexMergedIntoAsu(merged, validation.hand_op,
                                      validation.model_space_group_number, merge_friedel);
        space_group_number = validation.model_space_group_number;
        const gemmi::SpaceGroup *sg = gemmi::find_spacegroup_by_number(space_group_number);
        logger.Info("Model validation: the written reflections take the model's enantiomorph, {} ({}), "
                    "reindexed by {}", sg ? sg->short_name() : "?", space_group_number,
                    hkl_triplet(validation.hand_op));
    }

    // The alternative indexing, by contrast, is metric- and group-preserving: only the labels move.
    if (!(validation.indexing_op == gemmi::Op::identity())) {
        merged = ReindexMergedIntoAsu(merged, validation.indexing_op, space_group_number, merge_friedel);
        logger.Info("Model validation: the written reflections take the model's indexing, reindexed by {}",
                    hkl_triplet(validation.indexing_op));
    }
    return space_group_number;
}

std::vector<MergedReflection> ModelReferenceIntensities(const std::string &model_path,
                                                        const std::optional<UnitCell> &cell,
                                                        std::optional<int> space_group_number,
                                                        double d_min,
                                                        Logger &logger) {
    std::vector<MergedReflection> out;
    if (!(d_min > 0.0)) {
        logger.Warning("Model reference: no resolution limit to compute the model intensities to");
        return out;
    }

    gemmi::Structure st;
    try {
        st = gemmi::read_pdb(gemmi::MaybeGzipped(model_path));
    } catch (const std::exception &e) {
        logger.Error("Model reference: cannot read model {}: {}", model_path, e.what());
        return out;
    }
    if (st.models.empty() || !st.cell.is_crystal()) {
        logger.Error("Model reference: model {} has no atoms or no unit cell", model_path);
        return out;
    }

    // Put the model in the cell and group the run works in, where it knows them, so the reference is
    // indexed the way the data are. The correlation that consumes this matches on hkl, so a small cell
    // difference costs nothing; the space group is what has to agree.
    if (cell.has_value()) {
        const gemmi::UnitCell target = *cell;
        if (target.is_crystal()) {
            const gemmi::UnitCell old = st.cell;
            for (gemmi::Model &m : st.models)
                for (gemmi::Chain &ch : m.chains)
                    for (gemmi::Residue &r : ch.residues)
                        for (gemmi::Atom &a : r.atoms)
                            a.pos = target.orthogonalize(old.fractionalize(a.pos));
            st.cell = target;
        }
    }
    if (space_group_number.has_value())
        if (const gemmi::SpaceGroup *sg = gemmi::find_spacegroup_by_number(*space_group_number))
            st.spacegroup_hm = sg->xhm();
    const gemmi::SpaceGroup *sg = st.find_spacegroup();
    if (!sg) {
        logger.Error("Model reference: model {} has no usable space group", model_path);
        return out;
    }
    st.setup_cell_images();

    gemmi::DensityCalculator<Table, float> dc;
    dc.d_min = d_min;
    dc.rate = 1.5;
    dc.set_grid_cell_and_spacegroup(st);
    dc.set_refmac_compatible_blur(st.models[0]);
    dc.put_model_density_on_grid(st.models[0]);
    gemmi::AsuData<std::complex<float>> fcalc =
        gemmi::transform_map_to_f_phi(dc.grid, true).prepare_asu_data(dc.d_min, dc.blur, false, false, false);

    // Flat bulk solvent at the standard constants. Nothing here is fitted - there are no observations
    // yet - but without it the few lowest-resolution reflections are the largest and the most wrong,
    // and a correlation on raw intensities would be led by them.
    constexpr double K_SOL = 0.35;
    constexpr double B_SOL = 46.0;
    gemmi::SolventMasker masker(gemmi::AtomicRadiiSet::Refmac);
    gemmi::Grid<float> mask_grid;
    mask_grid.unit_cell = dc.grid.unit_cell;
    mask_grid.spacegroup = dc.grid.spacegroup;
    mask_grid.set_size_from_spacing(dc.requested_grid_spacing(), gemmi::GridSizeRounding::Up);
    masker.put_mask_on_grid(mask_grid, st.models[0]);
    gemmi::AsuData<std::complex<float>> fmask =
        gemmi::transform_map_to_f_phi(mask_grid, true).prepare_asu_data(dc.d_min, 0);

    std::unordered_map<long, std::complex<float>> mask_by_hkl;
    mask_by_hkl.reserve(fmask.v.size());
    for (const auto &hv : fmask.v)
        mask_by_hkl[hkl_key(hv.hkl)] = hv.value;

    const gemmi::UnitCell &ucell = st.cell;
    out.reserve(fcalc.v.size());
    for (const auto &hv : fcalc.v) {
        const double d = ucell.calculate_d(hv.hkl);
        if (!(d > 0.0))
            continue;
        std::complex<float> f = hv.value;
        const auto it = mask_by_hkl.find(hkl_key(hv.hkl));
        if (it != mask_by_hkl.end())
            f += static_cast<float>(K_SOL * std::exp(-B_SOL / (4.0 * d * d))) * it->second;
        const double F = std::abs(f);
        out.push_back(MergedReflection{.h = hv.hkl[0], .k = hv.hkl[1], .l = hv.hkl[2],
                                       .I = static_cast<float>(F * F),
                                       .d = static_cast<float>(d)});
    }

    logger.Info("Model reference: {} intensities computed from {} to {:.2f} A, space group {}",
                out.size(), model_path, d_min, sg->short_name());
    return out;
}