Normal mode analysis with molecular geometry restraints: Bridging molecular mechanics and elastic models

A new method for normal mode analysis is reported for all-atom structures using molecular geometry restraints (MGR). Similar to common molecular mechanics force fields, the MGR potential contains short- and long-range terms. The short-range terms are defined by molecular geometry, i.e., bond lengths, angles and dihedrals; the long-range term is similar to that in elastic network models. Each interaction term uses a single force constant parameter, and is determined by fitting against a set of known structures. Tests on proteins/non-proteins show that MGR can produce low frequency eigenvectors closer to all-atom force-field-based methods than conventional elastic network models. Moreover, the “tip effect”, found in low frequency eigenvectors in elastic network models, is reduced in MGR to the same level of the modes produced by force-field-based methods. The results suggest that molecular geometry plays an important role, in addition to molecular shape, in determining low frequency deformational motions. MGR does not require initial energy minimization, and is applicable to almost any structure, including the one with missing atoms, bad contacts, or bad geometries, frequently observed in low-resolution structure determination and refinement. The method bridges the two major representations in normal mode analyses, i.e., the molecular mechanics models and elastic network models.

Research highlights
► Normal mode analysis for all-atom structure using molecular geometry restraints (MGR).
► Eigenvectors closer to force-field-based methods than elastic network models.
► Reducing the “tip effect” to the same level of the force-field-based method.
► No initial energy minimization is required and applicable to any poor-quality structure.
► Showing the role of molecular geometry, in addition to shape, in forming low-frequency modes.