Investigation of human ß-defensins 1, 2 and 3 in human saliva by molecular dynamics.

Human ß-defensins present in saliva have a broad spectrum of antimicrobial activities that work against infections in oral cavity. To provide a better understanding of these molecules' properties and functions at the molecular level, we have investigated and compared the important structural properties of human ß-defensin-1, -2 and -3 using molecular dynamics simulations. Our results have shown that human ß-defensin-3 has a more flexible structure in water than the other two because of its high hydrophilicity, low ß-sheet content and high repulsive forces between its charged residues. Moreover, we found that the location of the salt bridges is important in protein's stability in water. Molecular dynamics simulations of human ß-defensins 1, 2 and 3 revealed that the hbd-3 is more flexible in water than hbd-1 and hbd-2.

Investigation of the effects of N-Acetylglucosamine on the stability of the spike protein in SARS-CoV-2 by molecular dynamics simulations.

A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. Nowadays, some researches study the role of the N-linked glycans as potential targets for vaccines and new agents. Due to the flexibility and diversity of the N-linked glycans, in this work, we focus on the N-Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. We performed molecular dynamics simulations to study the effects of the N-Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. After a 100 ns of simulation on the spike proteins without and with the N-Acetylglucosamine molecules, we found that the presence of N-Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. Thus; it can be inferred that the N-Acetylglucosamine moieties can potentially affect the interaction of the S protein with the ACE2 receptor. We also found that the S1 domain is more flexible than the S2 domain. We propose which of the experimentally observed glycans found on the spike may be more functional than the others. Detailed understanding of glycans is key for the development of new therapeutic strategies.

Amyloid inspired self-assembled peptide nanofibers.

Amyloid peptides are important components in many degenerative diseases as well as in maintaining cellular metabolism. Their unique stable structure provides new insights in developing new materials. Designing bioinspired self-assembling peptides is essential to generate new forms of hierarchical nanostructures. Here we present oppositely charged amyloid inspired peptides (AIPs), which rapidly self-assemble into nanofibers at pH 7 upon mixing in water caused by noncovalent interactions. Mechanical properties of the gels formed by self-assembled AIP nanofibers were analyzed with oscillatory rheology. AIP gels exhibited strong mechanical characteristics superior to gels formed by self-assembly of previously reported synthetic short peptides. Rheological studies of gels composed of oppositely charged mixed AIP molecules (AIP-1 + 2) revealed superior mechanical stability compared to individual peptide networks (AIP-1 and AIP-2) formed by neutralization of net charges through pH change. Adhesion and elasticity properties of AIP mixed nanofibers and charge neutralized AIP-1, AIP-2 nanofibers were analyzed by high resolution force-distance mapping using atomic force microscopy (AFM). Nanomechanical characterization of self-assembled AIP-1 + 2, AIP-1, and AIP-2 nanofibers also confirmed macroscopic rheology results, and mechanical stability of AIP mixed nanofibers was higher compared to individual AIP-1 and AIP-2 nanofibers self-assembled at acidic and basic pH, respectively. Experimental results were supported with molecular dynamics simulations by considering potential noncovalent interactions between the amino acid residues and possible aggregate forms. In addition, HUVEC cells were cultured on AIP mixed nanofibers at pH 7 and biocompatibility and collagen mimetic scaffold properties of the nanofibrous system were observed. Encapsulation of a zwitterionic dye (rhodamine B) within AIP nanofiber network was accomplished at physiological conditions to demonstrate that this network can be utilized for inclusion of soluble factors as a scaffold for cell culture studies.