The
physics-based potentials
of side-chain–side-chain interactions corresponding to pairs composed
of charged and polar, polar and polar, charged and hydrophobic, and hydrophobic and hydrophobic side chains have been determined. A total
of 144 four-dimensional potentials
of mean force (PMFs)
of all possible pairs
of molecules modeling these pairs were determined by umbrella-sampling molecular dynamics simulations in explicit water as functions
of distance and orientation, and the analytical expressions were then fitted to the PMFs. Depending on the type
of interacting sites, the analytical approximation to the PMF is a sum
of terms corresponding to van der Waals interactions and cavity-creation involving the nonpolar sections
of the side chains and van der Waals, cavity-creation, and electrostatic (charge–dipole or dipole–dipole) interaction energies and polarization energies involving the charged or polar sections
of the side chains. The model used in this work reproduces all features
of the interacting pairs. The
UNited RESidue force field with the new side-chain–side-chain interaction potentials was preliminarily tested with the N-terminal part
of the B-domain
of staphylococcal protein A (PDBL
1BDD; a three-α-helix bundle) and UPF0291 protein YnzC from Bacillus subtilis (PDB: 2HEP; an α-helical hairpin).