Molecular Simulation of Stapled Peptides

Victor Ovchinnikov; Aravinda Munasinghe; Martin Karplus

doi:10.1007/978-1-0716-1855-4_14

Molecular Simulation of Stapled Peptides

Methods Mol Biol. 2022:2405:283-301. doi: 10.1007/978-1-0716-1855-4_14.

Authors

Victor Ovchinnikov¹, Aravinda Munasinghe², Martin Karplus^{3

4}

Affiliations

¹ Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA. ovchinnv@georgetown.edu.
² Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
³ Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA. marci@tammy.harvard.edu.
⁴ Laboratoire de Chimie Biophysique, ISIS, Université de Strasbourg, Strasbourg, France. marci@tammy.harvard.edu.

PMID: 35298819
DOI: 10.1007/978-1-0716-1855-4_14

Abstract

Constrained peptides represent a relatively new class of biologic therapeutics, which have the potential to overcome several limitations of small-molecule drugs, and of designed antibodies. Because of their modest size, the rational design of such peptides is becoming increasingly amenable to computer simulation; multi-microsecond molecular dynamic (MD) simulations are now routinely possible on consumer-grade graphical processors (GPUs). Here, we describe the procedures for performing and analyzing MD simulations of hydrocarbon-stapled peptides using the CHARMM energy function, in isolation and in complex with a binding partner, to investigate their conformational properties and to compute changes in their binding affinity upon mutation.

Keywords: Binding free energy; MDM2; MMGBSA; Molecular dynamics; Peptide design; p53.

MeSH terms

Molecular Conformation
Molecular Dynamics Simulation*
Peptides* / chemistry

Substances

Peptides