The pathophysiological mechanism studies or structure-based drug design for therapeutic peptides often require characterization of the peptide-receptor interactions which can be experimentally expensive. Taking the advantage of computer-aided molecular modeling, we developed a new algorithm called receptor-residue mapping (RR-mapping) to tackle one key challenge, scoring of predicted models in peptide-protein docking. By performing all-atom molecular dynamics (MD) simulations with the receptor being soaked in a water box containing 0.5 moles of capped dipeptide of 20 natural amino acids (AA), the RR maps with probabilities of AAs interacting with a receptor’s surface residues can be obtained. Applying RR-mapping, we have constructed residue maps for the human immunoglobulin G’s FC region to compare the binding affinities of known peptides and suggested the design of novel peptides with higher affinities. We also used this method to identify promising peptide ligands which can interfere with the aggregation of amyloid-beta, an intrinsically disordered and highly-flexible protein crucially involved in the Alzheimer’s disease. RR-mapping turns out to successfully reveal the preferred amino acids each protein residue is likely to interact with and provides insightful information for re-ranking of docking-predicted peptide binding modes. Moreover, the application of RR-mapping can be further extended to protein-protein interaction studies and guide rational biologics drug design.

To improve prediction of peptide-protein interactions: Development and evaluation of RR-mapping algorithm

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.