CGRAP: A Web Server for Coarse-Grained Rigidity Analysis of Proteins

Elucidating protein rigidity offers insights about protein conformational changes. An understanding of protein motion can help speed drug development, and provide general insights into the dynamic behaviors of biomolecules. Existing rigidity analysis techniques employ fine-grained, all-atom modeling, which has a costly run-time, particularly for proteins made up of more than 500 residues. In this work, we introduce coarse-grained rigidity analysis, and showcase that it provides flexibility information about a protein that is similar in accuracy to an all-atom modeling approach. We assess the accuracy of the coarse-grained method relative to an all-atom approach via a comparison metric that reasons about the largest rigid clusters of the two methods. The apparent symmetry between the all-atom and coarse-grained methods yields very similar results, but the coarse-grained method routinely exhibits 40% reduced run-times. The CGRAP web server outputs rigid cluster information, and provides data visualization capabilities, including a interactive protein visualizer.

A Femoral Clamp to Reduce Soft Tissue Artifact: Accuracy and Reliability in Measuring Three-Dimensional Knee Kinematics During Gait

The accurate measurement of full six degrees-of-freedom (6DOFs) knee joint kinematics is prohibited by soft tissue artifact (STA), which remains the greatest source of error. The purpose of this study was to present and assess a new femoral clamp to reduce STA at the thigh. It was hypothesized that the device can preserve the natural knee joint kinematics pattern and outperform a conventional marker mounted rigid cluster during gait. Six healthy subjects were asked to walk barefoot on level ground with a cluster marker set (cluster gait) followed by a cluster-clamp-merged marker set (clamp gait) and their kinematics was measured using the cluster method in cluster gait and the cluster and clamp methods simultaneously in clamp gait. Two operators performed the gait measurement. A 6DOFs knee joint model was developed to enable comparison with the gold standard knee joint kinematics measured using a dual fluoroscopic imaging technique. One-dimensional (1D) paired t-tests were used to compare the knee joint kinematics waveforms between cluster gait and clamp gait. The accuracy was assessed in terms of the root-mean-square error (RMSE), coefficient of determination, and Bland–Altman plots. Interoperator reliability was assessed using the intraclass correlation coefficient (ICC). The result showed that the femoral clamp did not change the walking speed and knee joint kinematics waveforms. Additionally, clamp gait reduced the rotation and translation errors in the transverse plane and improved the interoperator reliability when compared to the rigid cluster method, suggesting a more accurate and reliable measurement of knee joint kinematics.

Gramicidin Lateral Distribution in Phospholipid Membranes: Fluorescence Phasor Plots and Statistical Mechanical Model

When using small mole fraction increments to study gramicidins in phospholipid membranes, we found that the phasor dots of intrinsic fluorescence of gramicidin D and gramicidin A in dimyristoyl-sn-glycero-3-phosphocholine (DMPC) unilamellar and multilamellar vesicles exhibit a biphasic change with peptide content at 0.143 gramicidin mole fraction. To understand this phenomenon, we developed a statistical mechanical model of gramicidin/DMPC mixtures. Our model assumes a sludge-like mixture of fluid phase and aggregates of rigid clusters. In the fluid phase, gramicidin monomers are randomly distributed. A rigid cluster is formed by a gramicidin dimer and DMPC molecules that are condensed to the dimer, following particular stoichiometries (critical gramicidin mole fractions, Xcr including 0.143). Rigid clusters form aggregates in which gramicidin dimers are regularly distributed, in some cases, even to superlattices. At Xcr, the size of cluster aggregates and regular distributions reach a local maximum. Before a similar model was developed for cholesterol/DMPC mixtures (Sugar and Chong (2012) J. Am. Chem. Soc. 134, 1164–1171) and here the similarities and differences are discussed between these two models.

Structure and bonding of IrB12−: converting a rigid boron B12 platelet to a Wankel motor

B12 is a rigid cluster with a high inner ring rotational energy barrier. However, doping it with Ir lowers the barrier significantly, transforming the IrB12− cluster in a Wankel motor.