Energy landscapes for proteins described by the UNRES coarse-grained potential

Patryk A Wesołowski; Adam K Sieradzan; Michał J Winnicki; John W R Morgan; David J Wales

doi:10.1016/j.bpc.2023.107107

Energy landscapes for proteins described by the UNRES coarse-grained potential

Biophys Chem. 2023 Dec:303:107107. doi: 10.1016/j.bpc.2023.107107. Epub 2023 Sep 12.

Authors

Patryk A Wesołowski¹, Adam K Sieradzan², Michał J Winnicki³, John W R Morgan⁴, David J Wales⁵

Affiliations

¹ Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. Electronic address: paw61@cam.ac.uk.
² Faculty of Chemistry, Gdansk University, Wita Stwosza 63, 80-308 Gdańsk, Poland.
³ Faculty of Chemistry, Gdansk University, Wita Stwosza 63, 80-308 Gdańsk, Poland; Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA; Intercollegiate Faculty of Biotechnology, University of Gdańsk and the Medical University of Gdańsk, Abrahama 58, 80-307 Gdańsk, Poland.
⁴ Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; Downing College, University of Cambridge, Regent St., Cambridge CB2 1DQ, UK.
⁵ Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK. Electronic address: dw34@cam.ac.uk.

PMID: 37862761
DOI: 10.1016/j.bpc.2023.107107

Abstract

The self-assembly of proteins is encoded in the underlying potential energy surface (PES), from which we can predict structure, dynamics, and thermodynamic properties. However, the corresponding analysis becomes increasingly challenging with larger protein sizes, due to the computational time required, which grows significantly with the number of atoms. Coarse-grained models offer an attractive approach to reduce the computational cost. In this Feature Article, we describe our implementation of the UNited RESidue (UNRES) coarse-grained potential in the Cambridge energy landscapes software. We have applied this framework to explore the energy landscapes of four proteins that exhibit native states involving different secondary structures. Here we have tested the ability of the UNRES potential to represent the global energy landscape of proteins containing up to 100 amino acid residues. The resulting potential energy landscapes exhibit good agreement with experiment, with low-lying minima close to the PDB geometries and to results obtained using the all-atom AMBER force field. The new program interfaces will allow us to investigate larger biomolecules in future work, using the UNRES potential in combination with all the methodology available in the computational energy landscapes framework.

Keywords: Energy landscape; Potential energy surface; Proteins; UNRES coarse-grained model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Molecular Dynamics Simulation
Protein Conformation
Protein Structure, Secondary
Proteins* / chemistry
Software*
Thermodynamics

Substances

Proteins