Physical Sciences and Mathematics Commons^™

Progress In The Prediction Of Pka Values In Proteins, Emil Alexov, Ernest L. Mehler, Nathan Baker, Antonio Baptista, Yong Huang, Francesca Milletti, Jens Erik Nielsen, Damien Farrell, Tommy Carstensen, Mats H.M. Olsson, Jana K. Shen, Jim Warwicker, Sarah Williams, J Michael Word

Publications

The pK_a-cooperative aims to provide a forum for experimental and theoretical researchers interested in protein pK_a values and protein electrostatics in general. The first round of the pK_a-cooperative, which challenged computational labs to carry out blind predictions against pK_as experimentally determined in the laboratory of Bertrand Garcia-Moreno, was completed and results discussed at the Telluride meeting (July 6–10, 2009). This article serves as an introduction to the reports submitted by the blind prediction participants that will be published in a special issue of PROTEINS: Structure, Function and Bioinformatics. …

Developing Hybrid Approaches To Predict Pka Values Of Ionizable Groups, Shawn Witham, Kemper Talley, Lin Wang, Zhe Zhang, Daquan Gao, Wei Yang, Emil Alexov

Publications

Accurate predictions of pKa values of titratable groups require taking into account all relevant processes associated with the ionization/deionization. Frequently, however, the ionization does not involve significant structural changes and the dominating effects are purely electrostatic in origin allowing accurate predictions to be made based on the electrostatic energy difference between ionized and neutral forms alone using a static structure. On another hand, if the change of the charge state is accompanied by a structural reorganization of the target protein, then the relevant conformational changes have to be taken into account in the pKa calculations. Here we report a hybrid …

Left Ventricular Assist Devices: Engineering Design Considerations, Marwan A. Simaan, Eduardo Divo, George Faragallah, Yu Wang

Publications

Patients with end-stage congestive heart failure awaiting heart transplantation often wait long periods of time (300 days or more on the average) before a suitable donor heart becomes available. The medical community has placed increased emphasis on the use of Left Ventricular Assist Devices or LVADs that can substitute for, or enhance, the function of the natural heart while the patient is waiting for the heart transplant (Poirier, 1997; Frazier & Myers, 1999). Essentially, a rotary LVAD is a pump that operates continuously directing blood from the left ventricle into the aorta by avoiding the aortic valve. Generally speaking, the …

A Missense Mutation In Clic2 Associated With Intellectual Disability Is Predicted By In Silico Modeling To Affect Protein Stability And Dynamics, Shawn Witham, Kyoko Takano, Charles Schwartz, Emil Alexov

Publications

Large-scale next generation resequencing of X chromosome genes identified a missense mutation in the CLIC2 gene on Xq28 in a male with X-linked intellectual disability (XLID) and not found in healthy individuals. At the same time, numerous nsSNPs (nonsynonomous SNP) have been reported in the CLIC2 gene in healthy individuals indicating that the CLIC2 protein can tolerate amino acid substitutions and be fully functional. To test the possibility that p.H101Q is a disease-causing mutation, we performed in silico simulations to calculate the effects of the p.H101Q mutation on CLIC2 stability, dynamics, and ionization states while comparing the effects obtained for …

Particle‐In‐Cell Simulation Of Incoherent Scatter Radar Spectral Distortions Related To Beam‐Plasma Interactions In The Auroral Ionosphere, M. A. Diaz, M. Oppenheim, J. L. Semeter, M. Zettergren

Publications

An electrostatic parallel particle‐in‐cell (EPPIC) code that allows for particle beam injections and multiple boundary conditions is used to investigate the beam‐plasma interaction and its manifestations in the incoherent scatter (IS) spectrum. Specifically, the code is used to investigate anomalous enhancements in the ion acoustic line through the destabilization of the plasma by injection (or precipitation) of low‐energy electron beams. This enhancement of the ion acoustic line is a form of IS distortion commonly observed in the vicinity of auroral arcs called the naturally enhanced ion‐acoustic line (NEIAL). Simulations confirm the parametric decay of Langmuir waves as a plausible mechanism, …

Turbulence And Wave Dynamics Across Gas–Liquid Interfaces, Shahrdad Sajjadi, Julian Hunt, Stephen Belcher, Derek Stretch, John Clegg

Publications

Mechanisms are reviewed here for the distortion of turbulent flows near thin density interfaces and their effects on transfer processes across them. Firstly the results of rapid distortion calculations show how the in homogeneous eddy structure depends on whether the turbulence is generated above or below the interface, or in both regions. The flow is unstratified and the buoyancy forces are stable and strong enough relative to the inertial forces that the interface is continuous. It is shown that as the surface blocks the vertical turbulent eddy motions, horizontal straining motions are induced which affect the surface viscous layers and …

On The Role Of Electrostatics In Protein–Protein Interactions, Zhe Zhang, Shawn Witham, Emil Alexov

Publications

The role of electrostatics in protein–protein interactions and binding is reviewed in this paper. A brief outline of the computational modeling, in the framework of continuum electrostatics, is presented and the basic electrostatic effects occurring upon the formation of the complex are discussed. The effect of the salt concentration and pH of the water phase on protein–protein binding free energy is demonstrated which indicates that the increase of the salt concentration tends to weaken the binding, an observation that is attributed to the optimization of the charge–charge interactions across the interface. It is pointed out that the pH-optimum (pH of …

In Silico And In Vitro Investigations Of The Mutability Of Disease-Causing Missense Mutation Sites In Spermine Synthase, Zhe Zhang, Joy Norris, Charles Schwartz, Emil Alexov

Publications

Background

Spermine synthase (SMS) is a key enzyme controlling the concentration of spermidine and spermine in the cell. The importance of SMS is manifested by the fact that single missense mutations were found to cause Snyder-Robinson Syndrome (SRS). At the same time, currently there are no non-synonymous single nucleoside polymorphisms, nsSNPs (harmless mutations), found in SMS, which may imply that the SMS does not tolerate amino acid substitutions, i.e. is not mutable.

Methodology/Principal Findings

To investigate the mutability of the SMS, we carried out in silico analysis and in vitro experiments of the effects of amino acid substitutions at the …

Observations On Braided Thin Wire Nucleate Boiling In Microgravity, Justin P. Koeln, Jeffrey C. Boulware, Heng Ban, Jr Dennison

Publications

A microgravity experiment was conducted on the Space Shuttle Endeavor (STS-108) to observe sustained nucleate boiling of water. Subcooled water was boiled with a single strand and a braid of three 0.16. mm diameter and 80. mm long Nichrome resistive wires. A CCD video camera recorded the experiment while six thermistors recorded the temperature of the fluid at various distances from the heating element. This paper reports experimental results in observations, measurements, and data analysis. Bubble explosions were found to take place shortly after the onset of boiling for both the single and braid of wires. The explosion may produce …