Virtual Screening of Human Serum Albumin Mutants to Optimize the Search for its Forms that Increase Affinity to Amyloid-Β Peptide

Abstract

A promising approach to the treatment of Alzheimer's disease (AD) is the removal of amyloid-β peptide (Aβ) from the patient's central nervous system by acting on human serum albumin (HSA). HSA carries 90% of Aβ in blood serum and 40-90% of Aβ in the cerebrospinal fluid (CNS). In this work, virtual screening of all possible mutant forms of HSA based on the data of the I-Mutant service made it possible to predict changes in HSA stability and identify the most “sensitive” regions of its polypeptide chain to substitutions. The data obtained will be used to optimize the search for HSA forms with increased affinity to Aβ, as well as to study the mechanisms underlying the modulating effects of HSA ligands on its interaction with Aβ, which can become the basis for the development of new approaches to therapy and prevention of AD.

Virtual Screening of Peptide Libraries: The Search for Peptide-Based Therapeutics Using Computational Tools

“…The critical role played by in silico tools for the discovery of novel bioactive peptides has been proved in different biomedical fields, such as the development of therapeutics against cancer or viral infections, immune system regulators, antidepressants, anxiolytics, analgesics, as well as peptides for the treatment of nicotine addiction, hypertension, Parkinson's disease, and neuropathic pains [101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119].…”

“…To treat AD, one possible tactic could rely on the modulation of human serum albumin (HSA) carrier properties to remove as much as possible of the amyloid-β peptide (Aβ) from the central nervous system of patients affected by this pathology. Intriguingly, virtual screening strategies have been exploited as well to define HSA variants with the highest affinity for the Aβ peptide and gain information useful for the future development of therapeutics against AD [119].…”