PT  - JOURNAL ARTICLE
AU  - Armando Díaz-Valle
AU  - José Marcos Falcón-González
AU  - Mauricio Carrillo-Tripp
TI  - Hot-spots and their contribution to the self-assembly of the viral capsid: <em>in-silico</em> prediction and analysis
AID  - 10.1101/723023
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 723023
4099  - http://biorxiv.org/content/early/2019/08/06/723023.short
4100  - http://biorxiv.org/content/early/2019/08/06/723023.full
AB  - In order to rationally design biopolymers that mimic biological functions, first, we need to elucidate the molecular mechanisms followed by nature. For example, the viral capsid is a macromolecular complex formed by self-assembled proteins which, in many cases, are biopolymers with an identical amino acid sequence. Specific protein-protein interactions drive the capsid self-assembly process, leading to several distinct protein interfaces. Following the hot-spot hypothesis, we propose a conservation-based methodology to identify those interface residues that are crucial elements on the self-assembly and thermodynamic stability of the capsid. We validate our predictions by computational free energy calculations using an atomic-scale molecular model of an icosahedral virus. Our results show that a single mutation in any of the hot-spots significantly perturbs the quaternary interaction, decreasing the absolute value of the binding free energy, without altering the tertiary structure. Our methodology can lead to a strategy to rationally modulate the capsid’s thermodynamic properties.CCMVCowpea Chlorotic Mottle VirusCPcapsid proteinWTwild-typeCOMcenter-of-massMDMolecular DynamicsSMDSteered Molecular Dynamics