SARS-CoV-2 is the pathogen responsible for COVID-19 that has claimed over six million lives as of July 2022. The severity of COVID-19 motivates a need to understand how it could evolve to escape potential treatments and to find ways to strengthen existing treatments. Here, we used the molecular modeling methods MD + FoldX and PyRosetta to study the SARS-CoV-2 spike receptor binding domain (S-RBD) bound to two neutralizing antibodies, B38 and CB6 and generated lists of antibody escape and antibody strengthening mutations. Our resulting watchlist contains potential antibody escape mutations against B38/CB6 and consists of 211/186 mutations across 35/22 S-RBD sites. Some of these mutations have been identified in previous studies as being significant in human populations (e.g., N501Y). The list of potential antibody strengthening mutations that are predicted to improve binding of B38/CB6 to S-RBD consists of 116/45 mutations across 29/13 sites. These mutations could be used to improve the therapeutic value of these antibodies.

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The human immunodeficiency virus (HIV) can infect nondividing cells by interacting with the host nuclear pore complex. The host nuclear pore protein NUP153 directly interacts with the HIV capsid to promote viral nuclear entry.

QM/MM calculations the current work is focused on introduction of polarized embedding QM/MM technique in CHARMM with the Psi4 QM package. Polarized embedding in QM/MM ensures much greater accuracy as it takes into account 1) polarization of QM electron density in presence of the polarized MM electrostatic model and 2) polarization of the MM electrostatic model by the QM electric field. This presents an iterative process, requiring a self-consistent field (SCF) approach to converge the polarization response between the QM and MM regions. Polarized embedding can be readily applied with the CHARMM Drude polarizable force field that accounts for electronic polarization by attaching an auxiliary particle to each polarizable atom via a harmonic spring. Implementation includes an SCFoptimizer for Drude particles to handle polarization of the MM region due to them QM electric field. The integrator routines in CHARMM required for conducting the simulations are modified accordingly to allow simulations using a full SCF treatment of polarization. Details of the implementation and application to model systems will be presented.

transform 4-androstenedione (AD) to1,4-androstadiene-3,17-dione (ADD). in this study, we investigated how the active site of KstD211 affected substrate specificity by protein modeling and site-directed mutagenesis. We found that Tyr116 played an important role in recognizing steroid substrates. The mutation of Tyr116 to Ile enhanced the conversion rate of 4AD from 54% to 87%, compared with KstD211. in a pilot-scale reaction, the productivity of ADD by converting 4-AD reached 3.32 g/L/h. Furthermore, our data also revealed that different F116 mutants exhibited distinct specificity for a variety of steroidal substrates. Therefore, our work has provided the potential application of to KstD211 to dehydrogenize steroids in pharmaceutical industry.