Folding Lennard-Jones proteins by a contact potential

TL;DR

This paper investigates approximating Lennard-Jones protein interactions with pairwise contact potentials, finding near-native structures can be achieved through optimized contact parameters and energy minimization, aiding protein folding predictions.

Contribution

It demonstrates that exact contact potential representation of Lennard-Jones interactions is impossible, but near-native conformations can be obtained using optimized contact parameters and energy minimization techniques.

Findings

Exact contact potential matching Lennard-Jones interactions is impossible.

Optimized contact parameters produce structures close to native conformations.

Using these structures as starting points, native folds are recovered with high probability.

Abstract

We studied the possibility to approximate a Lennard Jones interaction by a pairwise contact potential. First we used a Lennard-Jones potential to design off-lattice, protein-like heteropolymer sequences, whose lowest energy (native) conformations were then identified by Molecular Dynamics. Then we turned to investigate whether one can find a pairwise contact potential, whose ground states are the contact maps associated with these native conformations. We show that such a requirement cannot be satisfied exactly - i.e. no such contact parameters exist. Nevertheless, we found that one can find contact energy parameters for which an energy minimization procedure, acting in the space of contact maps, yields maps whose corresponding structures are close to the native ones. Finally we show that when these structures are used as the initial point of a Molecular Dynamics energy minimization process, the correct native folds are recovered with high probability.