Modifying the energy term and considering entropic contribution by IE method significantly improve accuracy of predicted binding free in MM/PBSA method.

Multiple-site mutated SARS-CoV-2 Delta and Omicron variants may trigger immune escape against existing monoclonal antibodies. Here, molecular dynamics simulations combined with the interaction entropy method reveal mechanism of Delta/Omicron to Bamlanivimab/Etesevimab. The result shows significantly reduced binding affinity variant for both antibodies, due introduction positively charged residues that greatly weaken their electrostatic interactions. Meanwhile, significant structural...

As pivotal effectors of antiviral immunity, natural killer (NK) cells are crucial for controlling the spread COVID-19. The nonstructural protein 13 SARS-CoV-2 can encode a viral peptide (Nsp13232-240) preventing human leukocyte antigen E (HLA-E) from recognizing inhibitory receptor NKG2A, thereby activating NK cells. underlying molecular mechanisms Nsp13232-240 remain unclear. Therefore, we compared interaction discrepancy between self-peptide and Nsp13232-240, theoretically predicting its...

Correct discrimination of native structure plays an important role in drug design. IE method significantly improves the performance MM/PB(GB)SA discriminating and decoy structures protein–ligand/protein systems Bcl-2 family.

The continuous spread of the newly emerged SARS-CoV-2 Omicron variant (B.1.1.529) has become an important reason for surge in COVID-19 infections. Its numerous mutated residues containing key sites on receptor-binding domain (RBD) undoubtedly pose new challenges epidemic control. Although preventive measures are becoming more sophisticated, effects mutations binding virus to receptor protein remain be elucidated. Here, we used molecular dynamics (MD) simulations investigate differences mode...

Convenient and efficient therapeutic agents are urgently needed to block the continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, mechanism for novel orally targeted SARS-CoV-2 main protease (Mpro) inhibitor S-217622 is revealed through a molecular dynamics simulation. The difference in movement modes S-217622-Mpro complex apo-Mpro suggested could inhibit motility intensity Mpro, thus maintaining their stable binding. Subsequent energy calculations showed...

Pocket prediction and drug screening against monomeric/dimeric M^pro under different protonation of Cys145/His41, Ritonavir Arbidol, which may be optimal drugs.

Hierarchical clustering tree of residues providing contributions to system binding based on the free energy specific for (A) Bcl-xL systems (B) Bcl-2 systems.

The SARS-CoV-2 Delta (B.1.617.2) variant was identified in India October 2020, and it has quickly become the mainstream strain with strong toxicity spread, posing great challenges to epidemic control. However, molecular mechanism of its powerful infectivity remains unclear. It is meaningful investigate process variant's receptor-binding domain (RBD) binding angiotensin-converting enzyme 2 (ACE2). Here, we performed three repeated dynamics simulations for each system avoid accidents, alanine...

Protein folding, vital to life and death, is the basis of biological physics. The information about protein folding process dynamics tremendous significance in protein-folding field, research pathways has attracted considerable attention. Here, four systems (1HOD, 2AJJ, 2DX3, 2RLG) are performed simulation starting from linear structures order investigate their mechanisms using classical molecular (MD) self-guided Langevin (SGLD), respectively. latter can increase low-frequency motion, which...

The binding affinity of camostat, gabexate, and nafamostat to TMPRSS2 shows great advantages, where presents two reasonable conformations (forward reverse directions) the forward one is more stable than reverse.

Inhibitors that competitively bind MDM2/MDMX can block the inhibition of P53 by and restart its tumor-suppressive effect. Molecular studies targeting inhibitors have always been a hot topic in anticancer drug design. Although numerous designed previously against MDM2/MDMX, their dual efficacy has not demonstrated, few assessed general causes affecting these inhibitors. Here, molecular dynamics simulations alanine scanning combined with interaction entropy method were employed to precisely...

The ongoing evolution of the Omicron lineage SARS-CoV-2 has led to emergence subvariants that pose challenges antibody neutralization. Understanding binding dynamics between receptor-binding domains (RBD) these spike and monoclonal antibodies (mAbs) is pivotal for elucidating mechanisms immune escape advancing development therapeutic antibodies. This study focused on RBD regions BA.2, BA.5, BF.7, XBB.1.5, employing molecular simulations unravel their with a panel six mAbs, subsequently...

Neuroinflammation plays a significant role in pathogenesis of hepatic encephalopathy (HE). Radiotracer [18F]PBR146 is used for in-vivo imaging neuroinflammation. Bifidobacterium (BIF) and fecal microbiota transplantation (FMT) are emerging as promising therapeutic approaches HE. The objective this study was to monitor compare the treatment efficiencies BIF FMT on neuroinflammation chronic HE rats [bile duct ligation (BDL) operation] by micro-PET/CT. Thirty were divided into Sham+NS, BDL+NS,...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic and serious impact on human life health.

Addressing the frequent emergence of SARS-CoV-2 mutant strains requires therapeutic approaches with innovative neutralization mechanisms. The targeting multivalent nanobodies can enhance potency and reduce risk viral escape, positioning them as promising drug candidates. Here, synergistic mechanisms two types are investigated deeply. Our research revealed that Fu2-1-Fu2-2 system exhibited significant synergy, whereas Sb#15-Sb#68 demonstrated antagonism, in which entropy was dominant...

Protein–DNA binding mechanisms in a complex manner are essential for understanding many biological processes. Over the past decades, numerous experiments and calculations have analyzed specificity of protein–DNA binding. However, accuracy free energy prediction multi-base DNA systems still needs to be improved. Fis is DNA-binding protein that regulates various transcription recombination reactions. In present work, we tested several methods predict based on this system find favorable scheme...