The Associative memory, Water mediated, Structure and Energy Model (AWSEM) is a coarse-grained protein force field. AWSEM contains physically motivated terms, such as hydrogen bonding, as well as a bioinformatically based local structure biasing term, which efficiently takes into account many-body effects that are modulated by the local sequence. When combined with appropriate local or global alignments to choose memories, AWSEM can be used to perform de novo protein structure prediction. Herein we present structure prediction results for a particular choice of local sequence alignment method based on short residue sequences called fragments. We demonstrate the model’s structure prediction capabilities for three levels of global homology between the target sequence and those proteins used for local structure biasing, all of which assume that the structure of the target sequence is not known. When there are no homologs in the database of structures used for local structure biasing, AWSEM calculations produce structural predictions that are somewhat improved compared with prior works using related approaches. The inclusion of a small number of structures from homologous sequences improves structure prediction only marginally but when the fragment search is restricted to only homologous sequences, AWSEM can perform high resolution structure prediction and can be used for kinetics and dynamics studies.
Proteins have evolved to use water to help guide folding. A physically motivated, nonpairwise-additive model of water-mediated interactions added to a protein structure prediction Hamiltonian yields marked improvement in the quality of structure prediction for larger proteins. Free energy profile analysis suggests that long-range water-mediated potentials guide folding and smooth the underlying folding funnel. Analyzing simulation trajectories gives direct evidence that water-mediated interactions facilitate native-like packing of supersecondary structural elements. Long-range pairing of hydrophilic groups is an integral part of protein architecture. Specific water-mediated interactions are a universal feature of biomolecular recognition landscapes in both folding and binding. W ater is intimately involved in protein folding (1-4). That proteins denature both on heating and cooling strongly implicates the involvement of water degrees of freedom. Kauzmann (5) correctly inferred from thermodynamics the hydrophobic layering characteristic of protein structure before protein structures were determined crystallographically. The kinetics of water exclusion is often considered in discussing mechanisms of protein folding, but again it is the avoidance of water in the final folded structure that is emphasized (1). Hydrophobicity patterns have long been a dominant consideration in predicting protein structure by using sequence data (6) and are basic in synthetic protein design (7). Nevertheless, the structured character of water has not been a paramount factor in most existing algorithms for structure prediction (8). These usually rely on effective pair potentials (9) or buried surface area terms to account for the free energy of burying hydrophobic residues (10).In this article, we hypothesize that specific water-mediated interactions help guide the folding process even before native contacts form. Using this idea we develop a bioinformatic, nonpairwise-additive interaction model accounting for water and show that it greatly improves the efficiency and accuracy of structure prediction for ␣-helical proteins. Analysis of folding trajectories with this potential strongly implicates the guiding role of long-range water-mediated interactions. Interestingly, we find here that long-range hydrophilic interactions, as distinct from hydrophobic interactions, also take center stage.The bioinformatic route to water-mediated potentials is difficult in several ways (for more directly physical approaches see ref. 11). Although bound water is visible in structures, localizing waters is more difficult than localizing main-chain atoms. Monomeric protein structures also have relatively few visible watermediated interactions. Our path to a water-mediated potential started with an energy landscape analysis of protein-protein interactions and a bioinformatic survey of interfaces in dimer structures (12, 13). We found that the often-used contact potentials (9) worked well to describe hydrophobic binding interfaces; however, hydrophilic interf...
Chemisorbed hydrogen and various intermediate hydrocarbon fragments play an important role in the important reaction of ethylene hydrogenation to ethane, which is catalyzed by Pt(111). As a first step toward building a theoretical mechanism of the ethylene hydrogenation process, binding site preferences and geometries of chemisorbed hydrogen, methyl, and ethyl on the Pt(111) surface are presented and rationalized. State-of-the-art Pseudopotential Planewave Density Functional Theory is employed for calculating accurate binding energies and geometries for the adsorbates. A comprehensive theory of hydrogen and methyl chemisorption on Pt (111) is developed with the help of Crystal Orbital Hamilton Population formalism within the extended Hückel molecular orbital theory. The symmetry properties of the surface Pt orbitals as well as the mixing of Pt s, p, and d orbitals in pure Pt is shown to be crucial in determining the strength of subsequent interaction with an adsorbate. It is suggested that hydrogen moves freely on the Pt(111) surface while the methyl and ethyl groups are essentially pinned on the atop position. Strong agostic interactions between C-H bonds and surface Pt are proposed for methyl and ethyl on higher symmetry sites. The different nature of chemisorption on Pt and Ni surfaces is speculated. Theoretical results presented in this paper are generally consistent with the available experimental data.
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