Academic literature on the topic 'Protein rigid fitting'

The General Structure Analysis System (GSAS)-II software package is a fully developed, open source, crystallographic data analysis system written almost entirely in Python. For powder diffraction, it encompasses the entire data analysis process beginning with 2-dimensonal image integration, peak selection, fitting and indexing, followed by intensity extraction, structure solution and ultimately Rietveld refinement, all driven by an intuitive graphical interface. Significant functionality of GSAS-II also can be scripted to allow it to be integrated into workflows or other software. For protein studies, it includes restraints on bond distances, angles, torsions, chiral volumes and coupled torsions (e.g. Ramachandran Φ/Ψ angles) each with graphical displays allowing visual validation. Each amino acid residue (and any ligands) can be represented by flexible rigid bodies with refinable internal torsions and optionally fully described TLS thermal motion. The least-squares algorithm invokes a Levenberg-Marquart minimization of a normalized double precision full matrix via Singular Value Decomposition providing fast convergence and high stability even for a large number of parameters. This paper will focus on the description of the flexible rigid body model of the protein and the details of the refinement algorithm.

Atomic force microscopy (AFM) can visualize functional biomolecules near the physiological condition, but the observed data are limited to the surface height of specimens. Since the AFM images highly depend on the probe tip shape, for successful inference of molecular structures from the measurement, the knowledge of the probe shape is required, but is often missing. Here, we developed a method of the rigid-body fitting to AFM images, which simultaneously finds the shape of the probe tip and the placement of the molecular structure via an exhaustive search. First, we examined four similarity scores via twin-experiments for four test proteins, finding that the cosine similarity score generally worked best, whereas the pixel-RMSD and the correlation coefficient were also useful. We then applied the method to two experimental high-speed-AFM images inferring the probe shape and the molecular placement. The results suggest that the appropriate similarity score can differ between target systems. For an actin filament image, the cosine similarity apparently worked best. For an image of the flagellar protein FlhAC, we found the correlation coefficient gave better results. This difference may partly be attributed to the flexibility in the target molecule, ignored in the rigid-body fitting. The inferred tip shape and placement results can be further refined by other methods, such as the flexible fitting molecular dynamics simulations. The developed software is publicly available.

Membrane contact sites (MCS) between organelles are proposed as nexuses for the exchange of lipids, small molecules, and other signals crucial to cellular function and homeostasis. Various protein complexes, such as the endoplasmic reticulum-mitochondrial encounter structure (ERMES), function as dynamic molecular tethers between organelles. Here, we report the reconstitution and characterization of subcomplexes formed by the cytoplasm-exposed synaptotagmin-like mitochondrial lipid-binding protein (SMP) domains present in three of the five ERMES subunits—the soluble protein Mdm12, the endoplasmic reticulum (ER)-resident membrane protein Mmm1, and the mitochondrial membrane protein Mdm34. SMP domains are conserved lipid-binding domains found exclusively in proteins at MCS. We show that the SMP domains of Mdm12 and Mmm1 associate into a tight heterotetramer with equimolecular stoichiometry. Our 17-Å-resolution EM structure of the complex reveals an elongated crescent-shaped particle in which two Mdm12 subunits occupy symmetric but distal positions at the opposite ends of a central ER-anchored Mmm1 homodimer. Rigid body fitting of homology models of these SMP domains in the density maps reveals a distinctive extended tubular structure likely traversed by a hydrophobic tunnel. Furthermore, these two SMP domains bind phospholipids and display a strong preference for phosphatidylcholines, a class of phospholipids whose exchange between the ER and mitochondria is essential. Last, we show that the three SMP-containing ERMES subunits form a ternary complex in which Mdm12 bridges Mmm1 to Mdm34. Our findings highlight roles for SMP domains in ERMES assembly and phospholipid binding and suggest a structure-based mechanism for the facilitated transport of phospholipids between organelles.

The capacity of palm oil production is directly affected by the ripeness of the fresh fruit bunches (FFB) upon harvesting. Conventional harvesting standards rely on rigid harvesting scheduling as well as the number of fruitlets that have loosened from the bunch. Harvesting is usually done every 10 to 14 days, and an FFB is deemed ready to be harvested if there are around 5 to 10 empty sockets on the fruit bunch. Technology aided by imaging techniques relies heavily on the color of the fruit bunch, which is highly dependent on the surrounding light intensities. In this study, Raman spectroscopy is used for ripeness classification of oil palm fruits, based on the molecular assignments extracted from the Raman bands between 1240 cm−1 and 1360 cm−1. The Raman spectra of 52 oil palm fruit samples which contain the fingerprints of different organic compounds were collected. Signal processing was applied to perform baseline correction and to reduce background noises. Characteristic data of the organic compounds were extracted through deconvolution and curve fitting processes. Subsequently, a correlation study between organic compounds was developed and eight hidden Raman peaks including protein, beta carotene, carotene, lipid, guanine/cytosine, chlorophyll-a, and tryptophan were successfully located. Through ANOVA statistical analysis, a total of six peak intensities from proteins through Amide III (β-sheet), beta-carotene, carotene, lipid, guanine/cytosine, and carotene and one peak location from lipid were found to be significant. An automated oil palm fruit ripeness classification system deployed with artificial neural network (ANN) using the seven signification features showed an overall performance of 97.9% accuracy. An efficient and accurate ripeness classification model which uses seven significant Raman peak features from the correlation analysis between organic compounds was successfully developed.

AbstractWe have carried out chemical shift perturbation titrations on three contrasting proteins. The resulting chemical shifts have been analysed to determine the best way to fit the data, and it is concluded that a simultaneous fitting of all raw shift data to a single dissociation constant is both the most accurate and the most precise method. It is shown that the optimal weighting of 15N chemical shifts to 1H chemical shifts is protein dependent, but is around the consensus value of 0.14. We show that chemical shift changes of individual residues can be fit to give residue-specific affinities. Residues with affinities significantly stronger than average are found in close contact with the ligand and are suggested to form a rigid contact surface, but only when the binding involves little conformational change. This observation may be of value in analysing binding and conformational change.

In flexible fitting, the high-resolution crystal structure of a molecule is deformed to optimize its position with respect to a low-resolution density map. Solving the flexible fitting problem entails answering the following questions: (A) How can the crystal structure be deformed? (B) How can the term "optimum" be defined? and (C) How can the optimization problem be solved? In this dissertation, we answer the above questions in reverse order. (C) We develop PFCorr, a non-uniform SO(3)-Fourier-based tool to efficiently conduct rigid-body correlations over arbitrary subsets of the space of rigid-body motions. (B) We develop PF2Fit, a rigid-body fitting tool that provides several useful definitions of the optimal fit between the crystal structure and the density map while using PFCorr to search over the space of rigid-body motions (A) We develop PF3Fit, a flexible fitting tool that deforms the crystal structure with a hierarchical domain-based flexibility model while using PF2Fit to optimize the fit with the density map. Our contributions help us solve the rigid-body and flexible fitting problems in unique and advantageous ways. They also allow us to develop a generalized framework that extends, breadth-wise, to other problems in computational structural biology, including rigid-body and flexible docking, and depth-wise, to the question of interpreting the motions inherent to the crystal structure. Publicly-available implementations of each of the above tools additionally provide a window into the technically diverse fields of applied mathematics, structural biology, and 3D image processing, fields that we attempt, in this dissertation, to span.
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This study seeks to develop novel multi-material and multi-layer pads that are comfortable to wear and effective in protecting body parts that are subject to blunt impact. The proposed body protection pad will address a safety issue prominent in elderly people, industry workers, law enforcement/military personnel, and sport players. Among the population of those people, blunt impact due to various causes such as falls, bullets, and blast waves reduce quality of life, increase the possibility of early death, and cause extremely high medical costs to incur. Protector pads represent a promising strategy for reducing impact force and preventing injuries in high-risk individuals. However, clinical efficacy has been limited by poor user compliance. Currently available protectors are made of either hard shells or soft thick pads. Some of them are made of Non-Newtonian materials that are believed to be very efficient but their effectiveness hasn’t been proved yet. Even though some available protectors can be effective if worn, most people who need protection are reluctant to wear bulky and heavy garments or rigid shells. Therefore, it is important to develop new body protectors that best combine each individual’s requirements of wearing comfort (flexible, light weight), ease of fitting (customized), ensured protection, and cost-effectiveness. The authors brought up many different design ideas and the most promising ones were selected and their effectiveness is investigated in detail. One of those pads utilizes dome shape top layer and thin fabric membrane component, such as Kevlar, that is very strong in tension but flexible in bending. Such design will make the pads excellent in dissipating shock energy and converting normal shock force to lateral direction to minimize the shock force transmitted to the body parts. Through computational simulations, these pads were proved to be very flexible in bending and torsion while strong and rigid in compression. In addition, suitable materials were identified, and it has been verified that such materials can be used to design a viable product(s) that is thin, light, and flexible for wearing comfort but strong in normal impact direction to protect the body. This paper reports a parametric study using computational analyses (finite element analyses) conducted for dome-shaped structures with various materials such as thermoplastic polyurethane (Ninjaflex® and Semiflex®), polyethylene, resin polyester, polylactic acid (PLA), resin epoxy, epoxy S-glass, and epoxy E-glass. Parametric 3D CAD models of the dome-shape structures were created with various combinations of layers such as dome shell only, dome with fabric (such as Kevlar) membrane, dome with fabric membrane and solid filler, and dome with fillers of auxetic structure. Then, key structural characteristics of protectors such as normal (compression), bending, and torsional stiffness were evaluated through static analyses of FEA models. Then, impact/shock analyses were conducted using multiphysics finite-element-analysis models to validate the results obtained from the static analyses. Advanced additive manufacturing techniques (3D printers) were used to build prototypes of the pads for tests. Dimensions and materials of the multi-layer pads are optimized for light weight and flexibility while keeping excellent shock absorption capability. The mechanism for ideal input force distribution or shunting are explained and suggested for designing protectors using various combinations of materials and layers to reduce the risk of injury. The results show that the dome-shape structure can be an effective component of optimized body protection pads using a combination of various materials.