Transfer Learning from Markov Models Leads to Efficient Sampling of Related Systems. J Phys Chem B. 2017 Sep 22;: Authors: Sultan MM, Pande VS Abstract We recently showed that the…
Read moreRelated Articles Modeling the mechanism of CLN025 beta-hairpin formation. J Chem Phys. 2017 Sep 14;147(10):104107 Authors: McKiernan KA, Husic BE, Pande VS Abstract Beta-hairpins are substructures found in proteins that…
Read moreUnder normal cellular conditions, the tumor suppressor protein p53 is kept at low levels in part due to ubiquitination by MDM2, a process initiated by binding of MDM2 to the intrinsically disordered transactivation domain (TAD) of p53. Many experimental and simulation studies suggest that disordered domains such as p53 TAD bind their targets nonspecifically before folding to a tightly associated conformation, but the microscopic details are unclear. Toward a detailed prediction of binding mech…
Read moreRelated Articles Identification of simple reaction coordinates from complex dynamics. J Chem Phys. 2017 01 28;146(4):044109 Authors: McGibbon RT, Husic BE, Pande VS Abstract Reaction coordinates are widely used throughout…
Read moreNa+/K+-ATPase transports Na+ and K+ ions across the cell membrane via an ion-binding site becoming alternatively accessible to the intra- and extracellular milieu by conformational transitions that confer marked changes in ion-binding stoichiometry and selectivity. To probe the mechanism of these changes, we used molecular simulation and free-energy perturbation approaches to identify probable protonation states of Na+- and K+-coordinating residues in E1P and E2P conformations of Na+/K+-ATPase…
Read moreDiscovery of novel brain permeable and G protein-biased beta-1 adrenergic receptor partial agonists for the treatment of neurocognitive disorders. PLoS One. 2017;12(7):e0180319 Authors: Yi B, Jahangir A, Evans AK, Briggs…
Read moreOpenMM 7: Rapid development of high performance algorithms for molecular dynamics. PLoS Comput Biol. 2017 Jul 26;13(7):e1005659 Authors: Eastman P, Swails J, Chodera JD, McGibbon RT, Zhao Y, Beauchamp KA,…
Read moreMolecular simulation has been used to model the detailed folding properties of peptides, yet prospective computational peptide design by such approaches remains challenging and nontrivial. To test the accuracy of simulation-based hairpin design, we characterized the folding properties of a series of so-called β-cap hairpin peptides designed to mimic a conserved hairpin of LapD, a bacterial intracellular signaling protein, both experimentally by NMR spectroscopy and computationally by implicit-…
Read moreIs Multitask Deep Learning Practical for Pharma? J Chem Inf Model. 2017 Jul 10;: Authors: Ramsundar B, Liu B, Wu Z, Verras A, Tudor M, Sheridan RP, Pande VS Abstract…
Read moreThe energy flow during natural photosynthesis is controlled by maintaining the spatial arrangement of pigments, employing helices as scaffolds. In this study, we have developed porphyrin-peptoid (pigment-helix) conjugates (PPCs) that can modulate the donor-acceptor energy transfer efficiency with exceptional precision by controlling the relative distance and orientation of the two pigments. Five donor-acceptor molecular dyads were constructed using zinc porphyrin and free base porphyrin (Zn(i …
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