Contact-based molecular dynamics of structured and disordered proteins in a coarse-grained model: Fixed contacts, switchable contacts and those described by pseudo-improper-dihedral angles

We present a coarse-grained Cα-based protein model that can be used to simulate structured, intrinsically disordered and partially disordered proteins. We use a Go-like potential for the structured parts and two different variants of a transferable potential for the disordered parts. The first variant uses dynamic structure-based (DSB) contacts that form and disappear quasi-adiabatically during the simulation. By using specific structural criteria we distinguish sidechain-sidechain, sidechain-backbone and backbone-backbone contacts. The second variant is a non-radial multi-body pseudo-improper-dihedral (PID) potential that does not include time-dependent terms but requires more computational resources. Our model can simulate in reasonable time thousands of residues on millisecond time scales. Program Title: cg CPC Library link to program files:https://doi.org/10.17632/dp7gwrs94n.1 Code Ocean capsule:https://codeocean.com/capsule/9528010 Licensing provisions: MIT Programming language: C++ (new version), Fortran (old version) Nature of problem: Simulations of one or more protein chains, structured, intrinsically disordered or partially disordered. Calculating their equilibrium and kinetic properties in processes including but not limited to: folding, aggregation, conformational changes, formation of complexes, aggregation, response to deformation. All those processes need long simulation times or many trajectories to properly sample the system. Solution method: The simulations use a molecular dynamics implicit-solvent coarse-grained model where each pseudoatom represents one amino acid residue. Residues are harmonically connected to form a chain. The system evolves according to Langevin dynamics. The backbone stiffness potential involves bond angle and dihedral angle terms (or a chirality term in the structured case). Residues interact via modified Lennard-Jones or Debye-Hueckel potentials. The potential is different for structured and disordered parts of a protein. A Go model contact map is used for the structured parts, where an interaction between two residues is attractive if effective spheres associated with their heavy atoms overlap in the native structure [1,2,3,4]. Non-attractive contacts use only the repulsive part of the Lennard-Jones potential. The potential for the disordered parts has two versions: in the quasi-adiabatic Dynamic Structure-Based (DSB) variant, the contacts are formed dynamically based on the structure of the chain and are quasi-a