Analyzing Internal Motion of Proteins From Viewpoint of Robot Kinematics: Formulation of Group Forced Response Method

2012 ◽  
Author(s):  
Keisuke Arikawa
Keyword(s):  
Protein Structures ◽  
Computational Cost ◽  
Three Dimensional ◽  
Structural Data ◽  
Simple Calculation ◽  
Forced Response ◽  
Internal Motion ◽  
Robot Kinematics ◽  
Internal Motions ◽  
Applied Forces

An analogous relationship exists between the kinematic structures of proteins and robotic mechanisms. Hence, using this analogy, we attempt to understand the internal motions of proteins from the perspective of robot kinematics. In this study, we propose a method called group forced response (GFR) method for predicting the internal motion of proteins on the basis of their three-dimensional structural data (PDB data). In this method, we apply forces in static equilibrium to groups of atoms (e.g., secondary structures, domains, and subunits) and not to specific atoms. Furthermore, we predict the internal motion of proteins by analyzing the relative motion caused among groups by the applied forces. First, we show a method for approximately modeling protein structures as a robotic mechanism and the basic kinematic equations of the model. Next, the GFR method is formulated (e.g., Jacobian matrix for group motions, magnitude of forces applied to groups, and decomposition of motions into modes according to structural compliances). Finally, we present example applications of the proposed method in real protein structures. Despite the approximations in the model, low computational cost, and use of simple calculation parameters, the results almost agree with measured internal motions.

Structural Compliance Analysis and Internal Motion Properties of Proteins From a Robot Kinematics Perspective: Formulation of Basic Equations

2016 ◽  
Vol 8 (2) ◽  
Author(s):  
Keisuke Arikawa
Keyword(s):  
Kinematic Model ◽  
Structural Data ◽  
Forced Response ◽  
Internal Motion ◽  
Robot Kinematics ◽  
Dihedral Angles ◽  
Protein Model ◽  
Applied Forces ◽  
Basic Equations ◽  
Structural Compliance

From a perspective of robot kinematics, we develop a method for predicting internal motion properties and understanding the functions of proteins from their three-dimensional (3D) structural data (protein data bank (PDB) data). The key ideas are based on the structural compliance analysis of proteins. In this paper, we mainly discuss the basic equations for the analysis. First, a kinematic model of a protein is introduced. Proteins are simply modeled as serial manipulators constrained by linear springs, where the dihedral angles on the main chains correspond to the joint angles of manipulators. Then, the kinematic equations of the protein model are derived. In particular, the forced response or the deformation caused by the forces in static equilibrium forms the basis for the structural compliance analysis. In the formulations, the protein models are regarded as manipulators that control the positions in the model or the distances between them, by the dihedral angles on the main chains. Next, the structural compliance of the protein model is defined, and a method for extracting the information about the internal motion properties from the structural compliance is shown. In general, the structural compliance refers to the relationship between the applied forces and the deformation of the parts surrounded by the application points. We define it in a more general form by separating the parts whose deformations are evaluated from those where forces are applied. When decomposing motion according to the magnitude of the structural compliance, we can infer that the lower compliance motion will easily occur. Finally, we show two application examples using PDB data of lactoferrin and hemoglobin. Despite using an approximate protein model, the predicted internal motion properties agree with the measured ones.

scholarly journals Protein Structure Determination in Living Cells

2019 ◽  
Vol 20 (10) ◽  
pp. 2442 ◽  
Author(s):  
Teppei Ikeya ◽  
Peter Güntert ◽  
Yutaka Ito
Keyword(s):  
Protein Structure ◽  
Structure Determination ◽  
Structure Prediction ◽  
Structural Information ◽  
Nuclear Overhauser Effect ◽  
Protein Structures ◽  
Three Dimensional ◽  
Structural Data ◽  
Sample Tube ◽  
In Cells

To date, in-cell NMR has elucidated various aspects of protein behaviour by associating structures in physiological conditions. Meanwhile, current studies of this method mostly have deduced protein states in cells exclusively based on ‘indirect’ structural information from peak patterns and chemical shift changes but not ‘direct’ data explicitly including interatomic distances and angles. To fully understand the functions and physical properties of proteins inside cells, it is indispensable to obtain explicit structural data or determine three-dimensional (3D) structures of proteins in cells. Whilst the short lifetime of cells in a sample tube, low sample concentrations, and massive background signals make it difficult to observe NMR signals from proteins inside cells, several methodological advances help to overcome the problems. Paramagnetic effects have an outstanding potential for in-cell structural analysis. The combination of a limited amount of experimental in-cell data with software for ab initio protein structure prediction opens an avenue to visualise 3D protein structures inside cells. Conventional nuclear Overhauser effect spectroscopy (NOESY)-based structure determination is advantageous to elucidate the conformations of side-chain atoms of proteins as well as global structures. In this article, we review current progress for the structure analysis of proteins in living systems and discuss the feasibility of its future works.

Kinematic Modeling and Internal Motion Analysis of Proteins From a Robot Kinematics Viewpoint

2011 ◽  
Author(s):  
Keisuke Arikawa
Keyword(s):  
Jacobian Matrix ◽  
Robot Manipulator ◽  
Kinematic Model ◽  
Internal Motion ◽  
Robot Kinematics ◽  
Kinematic Modeling ◽  
Serial Link ◽  
Internal Motions ◽  
Basic Equations ◽  
External Forces

This paper discusses the kinematic modeling of proteins and the analysis of their internal motion from the viewpoint of robot kinematics. First, a kinematic model of a protein is introduced. This model consists of multiple serial link mechanisms and interaction lines (lines between alpha carbons). The protein model is regarded as a type of a robot manipulator that uses joint angles to control the lengths of the interaction lines, and the Jacobian matrix of the manipulator is derived. On the basis of this Jacobian matrix, the basic equations for calculating the deformation caused by external forces and evaluating the structural compliance of specified parts are derived. Finally, by combining the derived basic equations, we analyze the internal motions of lactoferrin and hemoglobin and compare the results with the reported measured characteristics of their internal motions. Despite the approximations by the model, the results obtained by the proposed method agree with the measured internal motion.

Detection of Cracks in Mistuned Bladed Disks Using Reduced-Order Models and Vibration Data

2012 ◽  
Vol 134 (6) ◽  
Author(s):  
Chulwoo Jung ◽  
Akira Saito ◽  
Bogdan I. Epureanu
Keyword(s):  
Degrees Of Freedom ◽  
Dimensional Space ◽  
Equations Of Motion ◽  
Computational Cost ◽  
Three Dimensional ◽  
Cost Savings ◽  
Forced Response ◽  
Response Analysis ◽  
Reduced Order Models ◽  
Reduced Order

A novel methodology to detect the presence of a crack and to predict the nonlinear forced response of mistuned turbine engine rotors with a cracked blade and mistuning is developed. The combined effects of the crack and mistuning are modeled. First, a hybrid-interface method based on component mode synthesis is employed to develop reduced-order models (ROMs) of the tuned system with a cracked blade. Constraint modes are added to model the displacements due to the intermittent contact between the crack surfaces. The degrees of freedom (DOFs) on the crack surfaces are retained as active DOFs so that the physical forces due to the contact/interaction (in the three-dimensional space) can be accurately modeled. Next, the presence of mistuning in the tuned system with a cracked blade is modeled. Component mode mistuning is used to account for mistuning present in the uncracked blades while the cracked blade is considered as a reference (with no mistuning). Next, the resulting (reduced-order) nonlinear equations of motion are solved by applying an alternating frequency/time-domain method. Using these efficient ROMs in a forced response analysis, it is found that the new modeling approach provides significant computational cost savings, while ensuring good accuracy relative to full-order finite element analyses. Furthermore, the effects of the cracked blade on the mistuned system are investigated and used to detect statistically the presence of a crack and to identify which blade of a full bladed disk is cracked. In particular, it is shown that cracks can be distinguished from mistuning.

scholarly journals Novel Frame Model for Mistuning Analysis of Bladed Disk Systems

2017 ◽  
Vol 139 (3) ◽  
Author(s):  
Jie Yuan ◽  
Fabrizio Scarpa ◽  
Branislav Titurus ◽  
Giuliano Allegri ◽  
Sophoclis Patsias ◽  
...  
Keyword(s):  
Computational Cost ◽  
Three Dimensional ◽  
Maximum Amplitude ◽  
Forced Response ◽  
Full Scale ◽  
Fe Model ◽  
Response Dynamics ◽  
Frame Model ◽  
Bladed Disk ◽  
Beam Frame

The work investigates the application of a novel frame model to reduce computational cost of the mistuning analysis of bladed disk systems. A full-scale finite element (FE) model of the bladed disk is considered as benchmark. The frame configuration for a single blade is identified through structural identification via an optimization process. The individual blades are then assembled by three-dimensional (3D) springs, whose parameters are determined by means of a calibration process. The dynamics of the novel beam frame assembly is also compared to those obtained from three state-of-the-art FE-based reduced order models (ROMs), namely: a lumped parameter approach, a Timoshenko beam assembly, and component mode synthesis (CMS)-based techniques with free and fixed interfaces. The development of these classical ROMs to represent the bladed disk is also addressed in detail. A methodology to perform the mistuning analysis is then proposed and implemented. A comparison of the modal properties and forced response dynamics between the aforementioned ROMs and the full-scale FE model is presented. The case study considered in this paper demonstrates that the beam frame assembly can predict the variations of the blade amplitude factors, and the results are in agreement with full-scale FE model. The CMS-based ROMs underestimate the maximum amplitude factor, while the results obtained from beam frame assembly are generally conservative. The beam frame assembly is four times more computationally efficient than the CMS fixed-interface approach. This study proves that the beam frame assembly can efficiently predict the mistuning behavior of bladed disks when low-order modes are of interest.

scholarly journals Leveraging protein dynamics to identify cancer mutational hotspots in 3D-structures

2018 ◽  
Author(s):  
Sushant Kumar ◽  
Declan Clarke ◽  
Mark B. Gerstein
Keyword(s):  
Protein Dynamics ◽  
Large Scale ◽  
Protein Structures ◽  
Three Dimensional ◽  
Structural Data ◽  
Detection Methods ◽  
Hotspot Detection ◽  
Driver Genes ◽  
3D Structures ◽  
Mutational Hotspots

AbstractLarge-scale exome sequencing of tumors has enabled the identification of cancer drivers using recurrence and clustering-based approaches. Some of these methods also employ three-dimensional protein structures to identify mutational hotspots in cancer-associated genes. In determining such mutational clusters in structures, existing approaches overlook protein dynamics, despite the essential role of dynamics in protein functionality. In this work, we present a framework to identify driver genes using a dynamics-based search of mutational hotspot communities. After partitioning 3D structures into distinct communities of residues using anisotropic network models, we map variants onto the partitioned structures. We then search for signals of positive selection among these residue communities to identify putative drivers. We applied our method using the TCGA pan-cancer atlas missense mutation catalog. Overall, our analyses predict one or more mutational hotspots within the resolved structures of 434 genes. Ontological and pathway enrichment analyses implicate genes with predicted hotspots to be enriched in biological processes associated with tumor progression. Additionally, a comparison between our approach and existing hotspot detection methods that use structural data suggests that the inclusion of dynamics significantly increases the sensitivity of driver detection.

Detection of Cracks in Mistuned Bladed Disks Using Reduced Order Models and Vibration Data

2011 ◽  
Author(s):  
Chulwoo Jung ◽  
Akira Saito ◽  
Bogdan I. Epureanu
Keyword(s):  
Degrees Of Freedom ◽  
Dimensional Space ◽  
Equations Of Motion ◽  
Computational Cost ◽  
Three Dimensional ◽  
Cost Savings ◽  
Forced Response ◽  
Response Analysis ◽  
Reduced Order Models ◽  
Reduced Order

A novel methodology to detect the presence of a crack and to predict the nonlinear forced response of mistuned turbine engine rotors with a cracked blade and mistuning is developed. The combined effects of the crack and mistuning are modeled. First, a hybrid-interface method based on component mode synthesis is employed to develop reduced order models (ROMs) of the tuned system with a cracked blade. Constraint modes are added to model the displacements due to the intermittent contact between the crack surfaces. The degrees of freedom (DOFs) on the crack surfaces are retained as active DOFs so that the physical forces due to the contact/interaction (in the three-dimensional space) can be accurately modeled. Next, the presence of mistuning in the tuned system with a cracked blade is modeled. Component mode mistuning is used to account for mistuning present in the un-cracked blades while the cracked blade is considered as a reference (with no mistuning). Next, the resulting (reducedorder) nonlinear equations of motion are solved by applying an alternating frequency/time-domain method. Using these efficient ROMs in a forced response analysis, it is found that the new modeling approach provides significant computational cost savings, while ensuring good accuracy relative to full-order finite element analyses. Furthermore, the effects of the cracked blade on the mistuned system are investigated, and used to detect statistically the presence of a crack and to identify which blade of a full bladed disk is cracked. In particular, it is shown that cracks can be distinguished from mistuning.

Extension of the Kinematics-Based Method for Predicting the Motion of Proteins

2014 ◽  
Author(s):  
Keisuke Arikawa
Keyword(s):  
Computational Cost ◽  
Three Dimensional ◽  
Structural Data ◽  
Data Bank ◽  
Serial Manipulators ◽  
Protein Model ◽  
The Matrix ◽  
Basic Equations ◽  
Definition Of ◽  
Structural Compliance

On the basis of an analogy between the kinematic structures of proteins and robotic mechanisms, we have so far developed methods for predicting the internal motion of proteins from three-dimensional structural data in the protein data bank (PDB). With these methods, we model proteins as serial manipulators constrained by springs, and calculate the structural compliance of the protein model. In this study, toward more practical purposes, we reformulate and extend the existing methods by broadening the definition of structural compliance and reducing the number of variables for expressing the conformation of the model. The broadening is performed by separating the parts whose deformations are evaluated from those where forces are applied. This separation allows the calculation of the effective forces causing deformation in other specified parts. We also reduce the number of conformation variables from the consideration based on the algebraic structure of the basic equations. The size of the matrix whose inverse must be calculated is thus minimized, and the computational cost is reduced. We verify the effectiveness of these extensions by analyzing the PDB data of some proteins.

Investigation of Algorithms for Analyzing Protein Internal Motion From Viewpoint of Robot Kinematics

2010 ◽  
Author(s):  
Keisuke Arikawa
Keyword(s):  
Main Chain ◽  
Control Strategies ◽  
Three Dimensional ◽  
Internal Motion ◽  
Robot Kinematics ◽  
Redundant Manipulators ◽  
Serial Link ◽  
Protein Model ◽  
External Forces ◽  
And Control

We investigate various algorithms for analyzing the characteristics of the internal motion of proteins based on the analogies between their kinematic structures and robotic mechanisms. First, we introduce an artificial simple protein model, planar main chain (PMC), composed of a planar serial link mechanism to investigate the algorithms. Then, we develop algorithms for analyzing the conformational fluctuations by applying the manipulability analysis of robot manipulators and control strategies for redundant manipulators. Next, we develop algorithms for analyzing the conformational deformation caused by the external forces and to evaluate the compliances of the specified parts of proteins. Finally, we show that the proposed algorithms developed by using PMC models are applicable for the three dimensional main chain structures of real proteins, and may be used to analyze their characteristics of the internal motion. We also reveal some preliminary simulation results of the analysis of a real protein.

scholarly journals The ICON Single-Column Mode

Atmosphere ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 906
Author(s):  
Ivan Bašták Ďurán ◽  
Martin Köhler ◽  
Astrid Eichhorn-Müller ◽  
Vera Maurer ◽  
Juerg Schmidli ◽  
...  
Keyword(s):  
Data Storage ◽  
Model Development ◽  
Computational Cost ◽  
Three Dimensional ◽  
Shallow Convection ◽  
Modeling Framework ◽  
Additional Tool ◽  
Eddy Simulation ◽  
Single Column ◽  
Stratocumulus Clouds

The single-column mode (SCM) of the ICON (ICOsahedral Nonhydrostatic) modeling framework is presented. The primary purpose of the ICON SCM is to use it as a tool for research, model evaluation and development. Thanks to the simplified geometry of the ICON SCM, various aspects of the ICON model, in particular the model physics, can be studied in a well-controlled environment. Additionally, the ICON SCM has a reduced computational cost and a low data storage demand. The ICON SCM can be utilized for idealized cases—several well-established cases are already included—or for semi-realistic cases based on analyses or model forecasts. As the case setup is defined by a single NetCDF file, new cases can be prepared easily by the modification of this file. We demonstrate the usage of the ICON SCM for different idealized cases such as shallow convection, stratocumulus clouds, and radiative transfer. Additionally, the ICON SCM is tested for a semi-realistic case together with an equivalent three-dimensional setup and the large eddy simulation mode of ICON. Such consistent comparisons across the hierarchy of ICON configurations are very helpful for model development. The ICON SCM will be implemented into the operational ICON model and will serve as an additional tool for advancing the development of the ICON model.

Sign in / Sign up

Export Citation Format

Share Document