The protein-ligand binding affinity quantifies the strength between a protein and its ligand. Computer modeling simulations can be used to estimate or free energy using data- physics-driven methods combination thereof. Here we discuss purely physics-based sampling approach based on biased molecular dynamics simulations. Our proposed method generalizes simplifies previously suggested stratification strategies that use umbrella other enhanced with additional collective-variable-based...

Within the last 2 decades, severe acute respiratory syndrome coronaviruses 1 and (SARS-CoV-1 SARS-CoV-2) have caused two major outbreaks; yet, for reasons not fully understood, coronavirus disease 2019 pandemic by SARS-CoV-2 has been significantly more widespread than 2003 SARS epidemic SARS-CoV-1, despite striking similarities between these viruses. The SARS-CoV-1 spike proteins, both of which bind to host cell angiotensin-converting enzyme 2, implied be a potential source their...

Profilin-1 (PFN1) is a 140-amino-acid protein with two distinct binding sites-one for actin and one poly-L-proline (PLP). The best-described function of PFN1 to catalyze elongation polymerization. Thus far, eight DNA mutations in the gene encoding are associated human amyotrophic lateral sclerosis (ALS). We others recently showed that these (Gly118Val or G118V Cys71Gly C71G) cause ALS rodents. In vitro studies suggested Met114Thr Thr109Met behave abnormally neurotoxicity. mechanism by which...

Abstract YidC, a bacterial member of the YidC/Alb3/Oxa1 insertase family, mediates membrane protein assembly and insertion. Cytoplasmic loops are known to have functional significance in proteins such as YidC. Employing microsecond-level molecular dynamics (MD) simulations, we show that crystallographically unresolved C2 loop plays crucial role structural Bacillus halodurans YidC2. We modeled used all- atom MD simulations investigate YidC2 its apo form, both with without loop. The was found...

Human fibroblast growth factor (FGF) 1 or hFGF1 is a member of the FGF family that involved in various vital processes such as cell proliferation, differentiation, angiogenesis, and wound healing. hFGF1, which associated with low stability vivo, known to be stabilized by binding heparin sulfate, glycosaminoglycan aids protein activation its surface receptor. The poor thermal proteolytic stabilizing role have long been observed experimentally; however, mechanistic details these phenomena are...

Human acidic fibroblast growth factor (hFGF1) is an all beta-sheet protein that involved in the regulation of key cellular processes including cell proliferation and wound healing. hFGF1 known to aggregate when subjected thermal unfolding. In this study, we investigate equilibrium unfolding using a wide array biophysical biochemical techniques. Systematic analyses chemical denaturation data on variants (Q54P, K126N, R136E, K126N/R136E, Q54P/K126N, Q54P/R136E, Q54P/K126N/R136E) indicate...

The coronavirus spike protein, which binds to the same human receptor in both SARS-CoV-1 and 2, has been implied be a potential source of their differential transmissibility. However, mechanistic details protein binding its remain elusive at molecular level. Here, we have used an extensive set unbiased biased microsecond-level all-atom dynamics (MD) simulations 2 proteins determine dynamic behavior prefusion structure two viruses. Our results indicate that active form SARS-CoV-2 is more...

Abstract The protein-ligand binding affinity quantifies the strength between a protein and its ligand. Computer modeling simulations can be used to estimate or free energy using data- physics-driven methods combination thereof. Here, we discuss purely physics-based sampling approach based on biased molecular dynamics (MD) simulations. Our proposed method generalizes simplifies previously suggested stratification strategies that use umbrella (US) other enhanced with additional...

Abstract Lysenin is a pore-forming toxin, which self-inserts open channels into sphingomyelin containing membranes and known to be voltage regulated. The mechanistic details of its gating mechanism, however, remains elusive despite much recent efforts. Here, we have employed novel combination experimental computational techniques examine model for gating, that based on the existence an “effective electric dipole” inspired by reported structures lysenin. We support this mechanism observations...

ABSTRACT Human fibroblast growth factor (FGF) 1 or hFGF1 is a member of the FGF family that involved in various vital processes such as cell proliferation, differentiation, angiogenesis and wound healing. hFGF1, which associated with low stability vivo , known to be stabilized by binding heparin sulfate, glycosaminoglycan aids protein activation its surface receptor. The poor thermal proteolytic stabilizing role have long been observed experimentally; however, mechanistic details these...

The surface protein hemagglutinin (HA) of the influenza virus plays a pivotal role in facilitating viral infection by binding to sialic acid receptors on host cells. Its conformational state is pH-sensitive, impacting its receptor-binding ability and evasion immune response. In this study, we conducted extensive equilibrium microsecond-level all-atom molecular dynamics (MD) simulations HA explore influence low pH dynamics. Specifically, investigated impact protonation conserved histidine...

The surface protein hemagglutinin (HA) of the influenza virus plays a pivotal role in facilitating viral infection by binding to sialic acid receptors on host cells. Its conformational state is pH-sensitive, impacting its receptor-binding ability and evasion immune response. In this study, we conducted extensive equilibrium microsecond-level all-atom molecular dynamics (MD) simulations HA explore influence low pH dynamics. Specifically, investigated impact protonation conserved histidine...

ABSTRACT YidC, a bacterial member of the YidC/Alb3/Oxa1 insertase family, mediates membrane protein assembly and insertion. Cytoplasmic loops are known to have functional significance in proteins such as YidC. Employing microsecond-level molecular dynamics (MD) simulations, we show that crystallographically unresolved C2 loop plays crucial role structural Bacillus halodurans YidC2. We modeled used allatom MD simulations investigate YidC2 its apo form, both with without loop. The was found...

ABSTRACT The protein-ligand binding affinity quantifies the strength between a protein and its ligand. Computer modeling simulations can be used to estimate or free energy using data- physics-driven methods combination thereof. Here, we discuss purely physics-based sampling approach based on biased molecular dynamics (MD) simulations, which in spirit is similar stratification strategy suggested previously by Woo Roux. proposed methodology uses umbrella (US) with additional restraints...

The novel multidomain protein, cpSRP43, is a unique subunit of the post-translational chloroplast signal recognition particle (cpSRP) targeting pathway in higher plants. cpSRP responsible for and insertion light-harvesting chlorophyll a/b binding proteins (LHCPs) to thylakoid membrane. Upon emergence into stroma, LHCPs form soluble transit complex with heterodimer, which composed cpSRP43 cpSRP54. irreplaceable as chaperone their translocation membrane remarkable its ability dissolve...

Abstract The novel multidomain protein, cpSRP43, is a unique subunit of the post-translational chloroplast signal recognition particle (cpSRP) targeting pathway in higher plants. cpSRP responsible for and insertion light-harvesting chlorophyll a/b binding proteins (LHCPs) to thylakoid membrane. Nuclear-encoded LHCPs are synthesized cytoplasm then imported into chloroplast. Upon emergence stroma, form soluble transit complex with heterodimer, which composed cpSRP43 cpSRP54, 54 kDa homologous...