Folding and insertion thermodynamics of the transmembrane WALP peptide

The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA)$_n$(L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide's insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum---in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence.Comment: 12 pages, 5 figure

Direct Evidence for Aligned Binding of Cellulase Enzymes to Cellulose Surfaces

The conversion of biomass into green fuels and chemicals is of great societal interest. Engineers have been designing new cellulase enzymes for the breakdown of otherwise insoluble cellulose materials. A barrier to the rational design of new enzymes has been our lack of a molecular picture of how cellulase binding occurs. A critical factor is the attachment via the enzyme&rsquo;s carbohydrate binding module (CBM). To elucidate the structural and mechanistic details of cellulase adsorption, we have combined experimental data from sum frequency generation spectroscopy with molecular dynamics simulations to probe the equilibrium structure and surface alignment of a 14-residue peptide mimicking the CBM. The data show that binding is driven by hydrogen bonding and that tyrosine side chains within the CBM align the cellulase with the registry of the cellulose surface. Such an alignment is favorable for the translocation and effective cellulose breakdown and is therefore likely an important parameter for the design of novel enzymes. &nbsp;</p

Engineering the Interface Between Biomolecules, Solvents, and Surfaces Using Molecular Simulation

Presented on April 2, 2014 from 4-5 pm in room G011 of the Molecular Science and Engineering Building.Jim Pfaendtner obtained his B.S. in Chemical Engineering (2001) from the Georgia Institute of Technology and his PhD in Chemical Engineering (2007) from Northwestern University under the supervision of Professor Linda J. Broadbelt. He subsequently was a research associate at the Center for Biophysical Modeling and Simulation (University of Utah, USA) under the supervision of Distinguished Professor Gregory A. Voth. From 2007–2009 he was a National Science Foundation International Research Postdoctoral Fellow (NSF-IRFP) working in collaboration with Professor Dr. Michele Parrinello and Professor Voth. He joined the faculty of The University of Washington in 2009.Runtime: 59:24 minutesRational design of unique solvents and surfaces holds great potential for providing new ways to use biomolecules in engineering applications. Computational models such as molecular dynamics (MD) hold great potential for connecting the atomic scale to the mesoscale for a wide range of problems such as biocatalysis in ionic liquids or surface-driven self-assembly of designer peptides. Unfortunately, severe computational restrictions often limit wide-ranging use of these tools to their full potential. New multiscale modeling algorithms that are based on MD have been developed that can overcome these challenges, dramatically increasing the computer’s viability as a tool for computation-driven discovery. The first part of this talk will highlight how we are using simulations to study thermodynamic driving forces that lead to unique orientation and conformation of peptides on surfaces. The second part of the talk will discuss recent work from our group exploring how nonnative media like ionic liquids changes the equilibrium behavior of enzymes

Effect of Fluoroethylene Carbonate Additive on the Initial Formation of Solid Electrolyte Interphase on Oxygen Functionalized Graphitic Anode in Lithium Ion Batteries

The formation of a solid electrolyte interphase (SEI) at the electrode/electrolyte interface substantially affects the stability and lifetime of lithium-ion batteries (LIBs). One of the methods to improve the lifetime of LIBs is by the inclusion of additive molecules to stabilize the SEI. To understand the effect of additive molecules on the initial stage of SEI formation, we compare the decomposition and oligomerization reactions of a fluoroethylene carbonate (FEC) additive on a range of oxygen functionalized graphitic anode to those of an ethylene carbonate (EC) organic electrolyte. A series of density functional theory (DFT) calculations augmented by ab-initio molecular dynamics (AIMD) simulations reveal that EC decomposition on an oxygen functionalized graphitic (1120) edge facet through an SN2 mechanism is spontaneous, even in an uncharged cell. Decomposition of EC through an SN2 reaction pathway results in alkoxide species regeneration which is responsible for continual oligomerization along the graphitic surface. In contrast, FEC prefers to decompose through an SN1 pathway, which does not promote alkoxide regeneration. The ability of FEC as an additive to suppress alkoxide regeneration results in a smaller and thinner SEI layer that is more flexible towards lithium intercalation during the charging/discharging process. In addition, the presence of different oxygen functional groups at the surface of graphite dictates the oligomerization products and LiF formation in the SEI

The Composition of Oxygen Functional Groups on Graphite Surfaces

The types and compositions of oxygen functional groups on graphite surfaces are heavily subjected to the method in which the graphite is synthesized and processed in experiments, which makes the characterization difficult. The challenge even extends to the modeling of oxygenated graphite surfaces in computational studies. However, determination of both the types and composition of oxygen functional groups on graphite surfaces is of paramount importance as it plays a significantly important role in dictating the behaviors and performances of electrochemical systems. For example, the surface structure and composition of the graphitic anode used in lithium-ion batteries (LIBs) determines the quality of a solid electrolyte interphase (SEI) that forms at the electrode/electrolyte interface, which in turns substantially affects the stability and lifetime of the devices. To help predict the structure and the composition of the surface oxygen functional groups on graphite surfaces resulting from solution-based synthesis and modification processes, we analyze the adsorption of different oxygen functional groups at both edge and basal sites of graphite as a function of pH under which the solution-based processes may take place. A series of DFT calculations reveal that at room temperature and for a pH range from 0 to 14, the (112 ̅0) edge surface of graphite will be fully oxygenated, while the basal sites remain unsaturated. The oxygen functional groups at the edge sites are comprised of mostly hydroxyl and ketonic groups, with carboxyl and carbonyl groups are present only in small amounts. Furthermore, we observe transformation of carbonyl group into ketonic group in the presence of empty surface carbon sites, which further stabilize the graphite surface. Meanwhile, carboxyl groups are more stable when all surface sites within a carboxyl layer are all populated. We conclude that the population of oxygen groups that can be found at the edge surface of a graphite in the ascending order are carboxyl < carbonyl < hydroxyl < ketonic. On the contrary to the edge plane, a small amount of oxygen functional groups may be forced to adsorb on the basal surface upon application of an external potential. The adsorbed groups are found to prefer to cluster together on basal sites in a highly ordered fashion, while the edge surface does not show this preference for adsorption sites

Molecular Driving Forces in the Self-Association of Silaffin Peptide R5 from MD Simulations

The 19-residue silaffin-R5 peptide has been widely studied for its ability to precipitate uniform SiO2 particles through mild temperature and pH pathways, in the absence of any organic solvents. There is consensus that post-translational modification (PTM) of side chains has a large impact on the biomineralization process. Thus, it is imperative to understand the precise mechanisms that dictate the formation of SiO2 from R5 peptide, including the effects of PTM on peptide aggregation and peptide-surface adsorption. In this work, we use molecular dynamics (MD) simulations to study the aggregation of R5 dimer with multiple PTMs, with the presence of different ions in solution. Since this system has strong interactions with deep metastable states, we use parallel bias metadynamics with partitioned families to efficiently sample the different states of the system. We find that peptide aggregation is a prerequisite for biomineralization. We observe that the electrostatic interactions are essential in the R5 dimer aggregation; for wild type R5 that only has positively charged residues, phosphate ions HPO42- in the solution form a bridge between two peptides and are essential for peptide aggregation. Alternatively, the post translational modification phosphorylation, which renders neutral serine residues negative, enables R5 to aggregate without phosphate ion. The extent of phosphorylation and location of phosphorylated residues on R5 peptide results in different behavior and extent of aggregation - the aggregation trend of R5 peptide that we observe is in line with SiO2 precipitation observed in previous experimental studies, proving that peptide aggregation is a prerequisite for biomineralization