Mapping of mutation-sensitive sites in protein-like chains

TL;DR

This study uses a simple lattice model to analyze how the distribution of mutation-sensitive sites in protein-like chains depends on interaction matrix regularity, revealing patterns influenced by hydrophobic effects and collective interactions.

Contribution

It demonstrates how the distribution of mutation-sensitive sites varies with interaction matrix regularity and collective effects in a simplified protein model.

Findings

'Hot' sites are located at positions with maximum neighbors under hydrophobic-dominated interactions.

Adding randomness or nonlinearity shifts 'hot' sites towards less connected surface regions.

Collective effects influence the spatial distribution of mutation-sensitive sites.

Abstract

In this work we have studied, with the help of a simple on-lattice model, the distribution pattern of sites sensitive to point mutations ('hot' sites) in protein-like chains. It has been found that this pattern depends on the regularity of the matrix that rules the interaction between different kinds of residues. If the interaction matrix is dominated by the hydrophobic effect (Miyazawa Jernigan like matrix), this distribution is very simple - all the 'hot' sites can be found at the positions with maximum number of closest nearest neighbors (bulk). If random or nonlinear corrections are added to such an interaction matrix the distribution pattern changes. The rising of collective effects allows the 'hot' sites to be found in places with smaller number of nearest neighbors (surface) while the general trend of the 'hot' sites to fall into a bulk part of a conformation still holds.