2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023 (674-677)
АУТОР(И) / AUTHOR(S): Sebastjan Kralj, Milan Hodošček, Marko Jukić, Urban Bren
Е-АДРЕСА / E-MAIL: sebastjan.kralj1@um.si
DOI: 10.46793/ICCBI23.674K
САЖЕТАК / ABSTRACT:
Protein-protein interactions (PPI) are critical for cellular functions, host-pathogen dynamics and are crucial with drug design efforts. The interaction of proteins is dependent on the amino acid sequence of a protein as it determines its binding affinity to various molecules, including drugs, DNA, RNA, and proteins. Polymorphisms, natural DNA variations, affect PPIs by altering protein structure and stability. Computational chemistry is vital for the prediction of ligand-protein interactions through techniques such as docking and molecular dynamics and can elucidate the changes in energy associated with such mutations.
We present a user-friendly protocol that uses the INTE command of CHARMM to predict the effects of mutations on PPIs. This command-line tool automates mutation analysis and interaction energy estimation, is applicable to different ligand types (protein, DNA, RNA, ion, small molecule) and provides various other features. The energy values yield absolute and normalized heat maps that allow rapid identification of stabilizing and destabilizing mutations. Our protocol forms the basis for automated programs that facilitate studies of binding-altering mutations in host-pathogen, protein-protein, and drug-target interactions.
КЉУЧНЕ РЕЧИ / KEYWORDS:
Mutations, Drug design, CHARMM, Protein-protein interaction
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