Percentile-based spread: a more accurate way to compare crystallographic models

2010 ◽  
Vol 66 (9) ◽  
pp. 970-978 ◽  
Author(s):  
Edwin Pozharski
Keyword(s):  
Crystal Structures ◽  
Root Mean Square ◽  
Conformational Changes ◽  
Alternative Measure ◽  
Mean Square ◽  
Root Mean Square Distance ◽  
Average Variation ◽  
Model Ensembles ◽  
Mean Square Distance

The comparison of biomacromolecular crystal structures is traditionally based on the root-mean-square distance between corresponding atoms. This measure is sensitive to the presence of outliers, which inflate it disproportionately to their fraction. An alternative measure, the percentile-based spread (p.b.s.), is proposed and is shown to represent the average variation in atomic positions more adequately. It is discussed in the context of isomorphous crystal structures, conformational changes and model ensembles generated by repetitive automated rebuilding.

scholarly journals Potensi Sinamaldehid sebagai Anti Hiperpigmentasi secara In Silico

2021 ◽  
Vol 7 (2) ◽  
pp. 95-101
Author(s):  
Ni Made Gani Pratiwi ◽  
Ni Made Atika Saraswati ◽  
Ni Made Irma Febby Prasasti Dewi ◽  
Luh Pande Putu Tirta
Keyword(s):  
Root Mean Square ◽  
In Silico ◽  
Mean Square ◽  
Inhibitor Protein ◽  
Protein Target ◽  
Root Mean Square Distance ◽  
Mean Square Distance

Permasalahan kulit yang sering ditemui yaitu hiperpigmentasi yang terjadi akibat adanya sintesis melanin berlebihan yang menyebabkan penggelapan warna kulit. Hiperpigmentasi dapat diatasi dengan agen anti hiperpigmentasi yang beraktivitas dalam menghambat proses sintesis melanin. Sintesis melanin dapat dihambat dengan berbagai cara salah satunya dengan menghambat aktivitas tyrosinase. Tyrosinase merupakan enzim yang berperan dalam mengkatalisis proses biosintesis melanin. Sinamaldehid merupakan senyawa bahan alam banyak ditemukan pada tanaman Cinnamomum burmanni mempunyai aktivitas sebagai antioksidan. Penelitian ini bertujuan untuk mengetahui potensi sinamaldehid dalam menghambat tyrosinase yang akan dibandingkan dengan native liganya secara in silico. Uji in silico dilakukan secara docking molecular dengan tahapan yaitu preparasi dan optimasi sinamaldehid, preparasi tyrosinase serta validasi dan docking. Metode docking molecular telah dinyatakan valid karena RMSD (root mean square distance) yang diperoleh tidak lebih dari 3 Å. Analisis data dilakukan dengan melihat energi ikatan yang dihasilkan dan ikatan yang terbentuk antara senyawa dengan residu asam amino pada protein. Nilai energi ikatan yang diperoleh antara ikatan sinamaldehid dengan tyrosinase adalah-6,21 kkal/mol. Sedangkan energi ikatan antara tyrosinase dengan native ligandnya -4,79 kkal/mol. Hal tersebut menunjukkan afinitas dari sinamaldehid pada protein tyrosinase lebih besar dibandingkan native ligandnya, sehingga sinamaldehid dikatakan memiliki potensi sebagai anti hiperpigmentasi dengan mekanisme molecular berupa inhibitor protein target tyrosinase sehingga dapat menghambat aktivitas enzim tyrosinase.

How root-mean-square distance (r.m.s.d.) values depend on the resolution of protein structures that are compared

2003 ◽  
Vol 36 (1) ◽  
pp. 125-128 ◽  
Author(s):  
Oliviero Carugo
Keyword(s):  
Protein Structure ◽  
Root Mean Square ◽  
Protein Pair ◽  
Protein Structures ◽  
Structural Similarity ◽  
Protein Crystal ◽  
Mean Square ◽  
Root Mean Square Distance ◽  
Open Question ◽  
Mean Square Distance

The most popular estimator of structural similarity is the root-mean-square distance (r.m.s.d.) between equivalent atoms, computed after optimal superposition of the two structures that are compared. It is known that r.m.s.d. values do not depend only on conformational differences but also on other features, for example the dimensions of the structures that are compared. An open question is how they might depend on the accuracy of the experimentally determined protein structures. Given that the accuracy of the protein crystal structures is generally estimated through the crystallographic resolution, it is important to know the dependence of the r.m.s.d. on the crystallographic resolution of the two structures that are compared. 14458 protein structure pairs of identical sequence were compared and the resulting r.m.s.d. values were normalized to 100-residue length to avoid the bias introduced by the dependence of the r.m.s.d. values on the protein-pair dimensions. On average, smaller r.m.s.d. values are associated with protein structure pairs at better resolution and the r.m.s.d. values tend to increase if the two proteins that are compared have been refined at different resolutions. For crystallographic resolutions ranging between 1.6 and 2.9 Å, both relationships appear to be linear: r.m.s.d. = −0.73 + 0.48 resolution and delta_r.m.s.d. = 0.20 + 0.30 delta_resolution (`delta' indicating difference). Although the linearity of these relationships is not expected to hold outside the 1.6–2.9 Å resolution range, they are useful in making the r.m.s.d. values more reliable.

scholarly journals The Construction of Chimeric T-Cell Receptor with Spacer Base of Modeling Study of VHH and MUC1 Interaction

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Nazanin Pirooznia ◽  
Sadegh Hasannia ◽  
Majid Taghdir ◽  
Fatemeh Rahbarizadeh ◽  
Morteza Eskandani
Keyword(s):  
Root Mean Square ◽  
Conformational Changes ◽  
Cell Receptor ◽  
Dynamics Simulation ◽  
Specific Response ◽  
Conformational Structure ◽  
Mean Square ◽  
Chimeric Receptors ◽  
Cell Immunotherapy ◽  
And Function

Adaptive cell immunotherapy with the use of chimeric receptors leads to the best and most specific response against tumors. Chimeric receptors consist of a signaling fragment, extracellular spacer, costimulating domain, and an antibody. Antibodies cause immunogenicity; therefore, VHH is a good replacement for ScFv in chimeric receptors. Since peptide sequences have an influence on chimeric receptors, the effect of peptide domains on each other's conformation were investigated. CD3Zeta, CD28, VHH and CD8α, and FcgIIα are used as signaling moieties, costimulating domain, antibody, and spacers, respectively. To investigate the influence of the ligation of spacers on the conformational structure of VHH, models of VHH were constructed. Molecular dynamics simulation was run to study the influence of the presence of spacers on the conformational changes in the binding sites of VHH. Root mean square deviation and root mean square fluctuation of critical segments in the binding site showed no noticeable differences with those in the native VHH. Results from molecular docking revealed that the presence of spacer FcgIIα causes an increasing effect on VHH with MUC1 interaction. Each of the constructs was transformed into the Jurkat E6.1. Expression analysis and evaluation of their functions were examined. The results showed good expression and function.

scholarly journals The THE ROLE OF ASTAXANTHIN COMPARED WITH METFORMIN IN PREVENTING GLYCATED HUMAN SERUM ALBUMIN FROM POSSIBLE UNFOLDING: A MOLECULAR DYNAMIC STUDY

2019 ◽  
pp. 276-282
Author(s):  
SYAHPUTRA WIBOWO ◽  
SRI WIDYARTI ◽  
AKHMAD SABARUDIN ◽  
DJOKO WAHONO SOEATMADJI ◽  
SUTIMAN BAMBANG SUMITRO
Keyword(s):  
Diabetes Mellitus ◽  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Root Mean Square ◽  
Conformational Changes ◽  
Glycated Albumin ◽  
Mean Square ◽  
Discovery Studio ◽  
Significant Difference

Objectives: Albumin in diabetes mellitus undergoes conformational changes that affect the ability as an endogenous scavenger. Treatment with astaxanthin (ASX) expected to improve the function of albumin in case of diabetes mellitus. The objectives of this study are to compare the capability of ASX and metformin to prevent conformational changes on glycated albumin. Methods: Data mining is performed to obtain human serum albumin (HSA) (4K2C), glucose (79025), ASX (5281224), and metformin (4091). Data preparation used PyRx and Discovery Studio 2016 Client. PyRx is utilized for docking and analysis of receptor-ligand interactions with LigPlus and Discovery Studio 2016 Client. YASARA is used for molecular dynamics simulations with a running time of 15.000 ps. Results: A description of the glycated-HSA (gHSA) conformational changes that are bound to metformin has been successfully carried out. Changes that occur were unfolding and release of bonds in gHSA. Unfolding on gHSA includes the release of bonds between sites A and B. The root mean square deviation (RMSD) backbone value of metformin-gHSA shows a significant difference with gHSA at 8650 ps where gHSA showed 6.47 nm while the metformin-gHSA was 8.06 nm and continues to increase up to 15.72 nm at the end of the simulation. RMSD and root mean square fluctuation residues of gHSA which were interacted with ASX showed conditions close to normal HSA. In 11725 ps ASX-gHSA remained stable at 5.78 nm, whereas gHSA increased to 8.13 nm. gHSA at the end of the simulation showed a number of 9.052 nm while the normal HSA was 7.561 nm. Conclusion: This result indicated that ASX prevents gHSA from possible unfolding.

A refinement of the crystal structures of K2ReCl6, K2ReBr6, and K2PtBr6

1970 ◽  
Vol 48 (7) ◽  
pp. 1151-1154 ◽  
Author(s):  
H. D. Grundy ◽  
I. D. Brown
Keyword(s):  
Single Crystal ◽  
Crystal Structures ◽  
Root Mean Square ◽  
Mean Square ◽  
X Ray ◽  
Bond Lengths ◽  
Using Data

The crystal structures of K2ReCl6, K2ReBr6, and K2PtBr6 have been refined using data collected on a single-crystal X-ray diffractometer to give weighted agreement indices ranging from 0.026 to 0.054 for 75 to 90 nonequivalent reflections. The following bond lengths were obtained: Re—Cl = 235 pm, Re—Br = 248 pm, Pt—Br = 246 pm, K—Cl = 348 pm, and K—Br = 367 and 364 pm in the Re and Pt compounds, respectively. The differences in the root-mean-square angles of libration of the MX62− ions in these and a number of isomorphous crystals are discussed.

scholarly journals Understanding the Effect of Structural Diversity in WRKY Transcription Factors on DNA Binding Efficiency through Molecular Dynamics Simulation

Biology ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 83
Author(s):  
Akshay Singh ◽  
Ajay Kumar Sharma ◽  
Nagendra Kumar Singh ◽  
Humira Sonah ◽  
Rupesh Deshmukh ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Dna Binding ◽  
Root Mean Square ◽  
Conformational Changes ◽  
Higher Plants ◽  
Crop Improvement ◽  
Dynamics Simulation ◽  
Type I ◽  
Mean Square ◽  
Different Types

A precise understanding of the molecular mechanism involved in stress conditions has great importance for crop improvement. Biomolecules, such as WRKY proteins, which are the largest transcription factor family that is widely distributed in higher plants, plays a significant role in plant defense response against various biotic and abiotic stressors. In the present study, an extensive homology-based three-dimensional model construction and subsequent interaction study of WRKY DNA-binding domain (DBD) in CcWRKY1 (Type I), CcWRKY51 (Type II), and CcWRKY70 (Type III) belonging to pigeonpea, a highly tolerant crop species, was performed. Evaluation of the generated protein models was done to check their reliability and accuracy based on the quantitative and qualitative parameters. The final model was subjected to investigate the comparative binding analysis of different types of WRKY–DBD with DNA-W-box (a cis-acting element) by protein–DNA docking and molecular dynamics (MD) simulation. The DNA binding specificity with WRKY variants was scrutinized through protein–DNA interaction using the HADDOCK server. The stability, as well as conformational changes of protein–DNA complex, was investigated through molecular dynamics (MD) simulations for 100 ns using GROMACS. Additionally, the comparative stability and dynamic behavior of each residue of the WRKY–DBD type were analyzed in terms of root mean square deviation (RMSD), root mean square fluctuation (RMSF)values of the backbone atoms for each frame taking the minimized structure as a reference. The details of DNA binding activity of three different types of WRKY–DBD provided here will be helpful to better understand the regulation of WRKY gene family members in plants.

scholarly journals Identification of Phosphatidylinositol 3-kinase δ (PI3Kδ) Inhibitor: Pharmacophore-based Virtual Screening and Molecular Dynamics Simulation

2020 ◽  
Vol 20 (5) ◽  
pp. 1070
Author(s):  
Muhammad Arba ◽  
Malindo Sufriadin ◽  
Daryono Hadi Tjahjono
Keyword(s):  
Molecular Dynamics ◽  
Root Mean Square ◽  
Conformational Changes ◽  
Binding Free Energy ◽  
Pharmacophore Model ◽  
Dynamics Simulation ◽  
Mean Square ◽  
Phosphatidylinositol 3 Kinase ◽  
Pharmacophore Modelling ◽  
Phosphatidylinositol 3

Phosphatidylinositol 3-kinase δ (PI3Kδ) is a validated drug target for the treatment of cancer. The present study aims to search for new inhibitors of PI3Kδ by employing pharmacophore modelling using LigandScout Advanced 4.3 software. The three hydrogen bond acceptors and two hydrophobic features were proposed as a pharmacophore model using LASW1976 structure. The model was then validated using the Area Under Curve (AUC) of Receiver Operating Characteristic (ROC) and GH score. It was used to screen new molecules in the ZINC database, which resulted in 599 hits. All 599 hits were then docked into PI3Kδ protein, and five best hits were submitted to 50 ns molecular dynamics simulations. Each hit complexed with PI3Kδ underwent minor conformational changes as indicated by the values of Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF). Furthermore, prediction of the binding free energy using Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA) method showed that five hits, i.e., Lig25/ZINC253496376, Lig682/ZINC98047241, Lig449/ZINC85878047, Lig554/ZINC253389510, and Lig199/ZINC12638303, had lower binding energy compared to LASW1976. This result indicated their potentials as new inhibitors of PI3Kδ.

Understanding the Binding Mechanism of Antagonist (AZD3293) Against BACE-1: Molecular Insights into Alzheimer’s Drug Discovery

2020 ◽  
Vol 17 (7) ◽  
pp. 850-857
Author(s):  
Sphelele Sosibo ◽  
Daniel Gyamfi Amoako ◽  
Anou Moise Somboro ◽  
Darren Delai Sun ◽  
Jane Catherine Ngila ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Root Mean Square ◽  
Conformational Changes ◽  
Radius Of Gyration ◽  
Mean Square ◽  
Binding Mechanism ◽  
Ligand Complex ◽  
Bace 1

Background: β-site amyloid precursor protein cleaving enzyme (BACE 1) is the ratelimiting enzyme in the formation of neurotoxic β-amyloid (Aβ) residues (Aβ1-40 or Aβ1-42) considered as key players in the onset of Alzheimer’s Disease (AD). Consequently, BACE 1 is one of the principal targets of anti-AD therapy with many small molecule BACE 1 inhibitors (BACE 1Is) in clinical trials. AZD3293 (Lanabecestat) is a BACE 1I that concluded in phase 2/3 clinical trials. Due to the limited knowledge about the interaction of this drug with the BACE 1 enzyme, in the present study, we performed comprehensive Molecular Dynamics (MD) analysis to understand the binding mechanism of AZD3293 to BACE 1. Methods: A production run of 120 ns is carried out and results are analysed using Root Mean Square Deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) to explain the stability of enzyme ligand complex. Further, the distance (d1) between the flap tip (Thr72) and the hinge residue of the flexible loop (Thr328), in relation to θ1 (Thr72–Asp228- Thr328), and to the dihedral angle δ (Thr72-Asp35-Asp228-Thr328) were measured. Results: The presence of the ligand within the active site restricted conformational changes as shown by decreased values of RMSF and average RMSD of atomic positions when compared to the values of the apoenzyme. Further analysis via the flap dynamics approach revealed that the AZD3293 decreases the flexibility of binding residues and made them rigid by altering the conformational changes. Conclusion: The prospective binding modes of AZD3293 from this study may extend the knowledge of the BACE 1-drug interaction and pave the way to design analogues with similar inhibitory properties needed to slow the progression of Alzheimer’s disease.

scholarly journals Effects of an Electric Field on the Conformational Transition of the Protein: Pulsed and Oscillating Electric Fields with Different Frequencies

Polymers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 123
Author(s):  
Qun Zhang ◽  
Dongqing Shao ◽  
Peng Xu ◽  
Zhouting Jiang
Keyword(s):  
Dipole Moment ◽  
Secondary Structure ◽  
Electric Field ◽  
Root Mean Square ◽  
Structure Analysis ◽  
Electric Fields ◽  
Conformational Changes ◽  
Pulsed Electric Field ◽  
Mean Square ◽  
Secondary Structure Analysis

The effect of pulsed and oscillating electric fields with different frequencies on the conformational properties of all-α proteins was investigated by molecular dynamics simulations. The root mean square deviation, the root mean square fluctuation, the dipole moment distribution, and the secondary structure analysis were used to assess the protein samples’ structural characteristics. In the simulation, we found that the higher frequency of the electric field influences the rapid response to the secondary structural transitions. However, the conformational changes measured by RMSD are diminished by applying the electrical field with a higher frequency. During the dipole moment analysis, we found that the magnitude and frequency of the dipole moment was directly related to the strength and frequency of the external electric field. In terms of the type of electric fields, we found that the average values of RMSD and RMSF of whole molecular protein are larger when the protein is exposed in the pulsed electric field. Concerning the typical sample 1BBL, the secondary structure analysis showed that two alpha-helix segments both transit to turns or random coils almost simultaneously when it is exposed in a pulsed electric field. Meanwhile, two segments present the different characteristic times when the transition occurs in the condition of an oscillating electric field. This study also demonstrated that the protein with fewer charged residues or more residues in forming α-helical structures display the higher conformational stability. These conclusions, achieved using MD simulations, provide a theoretical understanding of the effect of the frequency and expression form of external electric fields on the conformational changes of the all-α proteins with charged residues and the guidance for anticipative applications.

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