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

Molecular Simulation of Stapled Peptides

Victor Ovchinnikov  1 , Aravinda Munasinghe  2 , Martin Karplus  3   4
Affiliations

Molecular Simulation of Stapled Peptides

Victor Ovchinnikov et al. Methods Mol Biol. 2022.

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.

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References

    1. Fosgerau K, Hoffmann T (2015) Peptide therapeutics: current status and future directions. Drug Discov Today 20(1):122–128. https://doi.org/10.1016/j.drudis.2014.10.003 - DOI
    1. Cornillie S, Bruno B, Lim C, Cheatham T (2018) Computational modeling of stapled peptides toward a treatment strategy for CML and broader implications in the design of lengthy peptide therapeutics. J Phys chemistry B 122(14):3864–3875. https://doi.org/10.1021/acs.jpcb.8b01014 - DOI
    1. Verdine GL, Hilinski GJ (2012) Stapled peptides for intracellular drug targets., vol 503, 1st edn. Elsevier Inc., Amsterdam. https://doi.org/10.1016/B978-0-12-396962-0.00001-X
    1. Friedrichs M, Eastman P, Vaidyanathan V, Houston M, Legrand S, Beberg A, Ensign D, Bruns C, Pande V (2009) Accelerating molecular dynamic simulation on graphics processing units. J Comput Chem 30:864–872 - DOI
    1. Brooks B, Brooks III C, Mackerell Jr A, Nilsson L, Petrella R, Roux B, Won Y, Archontis G, Bartels C, Boresch S, et al (2009) CHARMM: the biomolecular simulation program. J Comput Chem 30:1545–1614, pMC2810661

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