scholarly journals AMPLE: a cluster-and-truncate approach to solve the crystal structures of small proteins using rapidly computedab initiomodels

2012 ◽  
Vol 68 (12) ◽  
pp. 1622-1631 ◽  
Author(s):  
Jaclyn Bibby ◽  
Ronan M. Keegan ◽  
Olga Mayans ◽  
Martyn D. Winn ◽  
Daniel J. Rigden
Keyword(s):  
Ab Initio ◽  
Crystal Structures ◽  
Sequence Data ◽  
Data File ◽  
Test Cases ◽  
Molecular Replacement ◽  
Computational Pipeline ◽  
Small Proteins ◽  
Sequence File ◽  
Local Accuracy

Proteinab initiomodels predicted from sequence data alone can enable the elucidation of crystal structures by molecular replacement. However, the calculation of suchab initiomodels is typically computationally expensive. Here, a computational pipeline based on the clustering and truncation of cheaply obtainedab initiomodels for the preparation of structure ensembles is described. Clustering is used to select models and to quantitatively predict their local accuracy, allowing rational truncation of predicted inaccurate regions. The resulting ensembles, with or without rapidly added side chains, solved 43% of all test cases, with an 80% success rate for all-α proteins. A program implementing this approach,AMPLE, is included in theCCP4 suite of programs. It only requires the input of aFASTAsequence file and a diffraction data file. It carries out the modelling using locally installedRosetta, creates search ensembles and automatically performs molecular replacement and model rebuilding.

SIR99, a program for the automatic solution of small and large crystal structures

1999 ◽  
Vol 55 (6) ◽  
pp. 991-999 ◽  
Author(s):  
Maria Cristina Burla ◽  
Mercedes Camalli ◽  
Benedetta Carrozzini ◽  
Giovanni Luca Cascarano ◽  
Carmelo Giacovazzo ◽  
...  
Keyword(s):  
Ab Initio ◽  
Crystal Structures ◽  
Prior Information ◽  
Flow Diagram ◽  
Large Crystal ◽  
Large Molecules ◽  
Small Proteins ◽  
Practical Information ◽  
User Intervention

The moduli and flow diagram of the program SIR99 are described. New phasing algorithms are proposed working both in direct and in reciprocal space. Their cooperative work is able to solve the structures of both small and large molecules. In particular, small proteins can be solved ab initio without any use of prior information and any user intervention. The efficiency of the various algorithms employed by SIR99 has been tested, and the role of the tangent formula clarified. The user is also provided with some practical information concerning the computer power needed.

scholarly journals Ab initio solution of macromolecular crystal structures without direct methods

2017 ◽  
Vol 114 (14) ◽  
pp. 3637-3641 ◽  
Author(s):  
Airlie J. McCoy ◽  
Robert D. Oeffner ◽  
Antoni G. Wrobel ◽  
Juha R. M. Ojala ◽  
Karl Tryggvason ◽  
...  
Keyword(s):  
Ab Initio ◽  
Crystal Structures ◽  
Signal To Noise Ratio ◽  
Direct Methods ◽  
Molecular Replacement ◽  
Signal To Noise ◽  
Model Quality ◽  
Theoretical Understanding ◽  
Unknown Structure ◽  
Noise Ratio

The majority of macromolecular crystal structures are determined using the method of molecular replacement, in which known related structures are rotated and translated to provide an initial atomic model for the new structure. A theoretical understanding of the signal-to-noise ratio in likelihood-based molecular replacement searches has been developed to account for the influence of model quality and completeness, as well as the resolution of the diffraction data. Here we show that, contrary to current belief, molecular replacement need not be restricted to the use of models comprising a substantial fraction of the unknown structure. Instead, likelihood-based methods allow a continuum of applications depending predictably on the quality of the model and the resolution of the data. Unexpectedly, our understanding of the signal-to-noise ratio in molecular replacement leads to the finding that, with data to sufficiently high resolution, fragments as small as single atoms of elements usually found in proteins can yield ab initio solutions of macromolecular structures, including some that elude traditional direct methods.

scholarly journals Routine phasing of coiled-coil protein crystal structures withAMPLE

IUCrJ ◽  
2015 ◽  
Vol 2 (2) ◽  
pp. 198-206 ◽  
Author(s):  
Jens M. H. Thomas ◽  
Ronan M. Keegan ◽  
Jaclyn Bibby ◽  
Martyn D. Winn ◽  
Olga Mayans ◽  
...  
Keyword(s):  
Ab Initio ◽  
Crystal Structures ◽  
Coiled Coil ◽  
Protein Crystal ◽  
Molecular Replacement ◽  
Search Models ◽  
Homologous Protein ◽  
Coil Structure ◽  
Convenient Route ◽  
Chain Lengths

Coiled-coil protein folds are among the most abundant in nature. These folds consist of long wound α-helices and are architecturally simple, but paradoxically their crystallographic structures are notoriously difficult to solve with molecular-replacement techniques. The programAMPLEcan solve crystal structures by molecular replacement usingab initiosearch models in the absence of an existent homologous protein structure.AMPLEhas been benchmarked on a large and diverse test set of coiled-coil crystal structures and has been found to solve 80% of all cases. Successes included structures with chain lengths of up to 253 residues and resolutions down to 2.9 Å, considerably extending the limits on size and resolution that are typically tractable byab initiomethodologies. The structures of two macromolecular complexes, one including DNA, were also successfully solved using their coiled-coil components. It is demonstrated that both theab initiomodelling and the use of ensemble search models contribute to the success ofAMPLEby comparison with phasing attempts using single structures or ideal polyalanine helices. These successes suggest that molecular replacement withAMPLEshould be the method of choice for the crystallographic elucidation of a coiled-coil structure. Furthermore,AMPLEmay be able to exploit the presence of a coiled coil in a complex to provide a convenient route for phasing.

scholarly journals Quantum Mechanical-Based Stability Evaluation of Crystal Structures for HIV-Targeted Drug Cabotegravir

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7178
Author(s):  
Yanqiang Han ◽  
Hongyuan Luo ◽  
Qianqian Lu ◽  
Zeying Liu ◽  
Jinyun Liu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ab Initio ◽  
Crystal Structures ◽  
Structure Prediction ◽  
Hiv Infections ◽  
Integrase Inhibitor ◽  
Hiv Integrase ◽  
Stability Evaluation ◽  
The Stability ◽  
Long Acting

The long-acting parenteral formulation of the HIV integrase inhibitor cabotegravir (GSK744) is currently being developed to prevent HIV infections, benefiting from infrequent dosing and high efficacy. The crystal structure can affect the bioavailability and efficacy of cabotegravir. However, the stability determination of crystal structures of GSK744 have remained a challenge. Here, we introduced an ab initio protocol to determine the stability of the crystal structures of pharmaceutical molecules, which were obtained from crystal structure prediction process starting from the molecular diagram. Using GSK744 as a case study, the ab initio predicted that Gibbs free energy provides reliable further refinement of the predicted crystal structures and presents its capability for becoming a crystal stability determination approach in the future. The proposed work can assist in the comprehensive screening of pharmaceutical design and can provide structural predictions and stability evaluation for pharmaceutical crystals.

X-ray Crystal Structures and ab Initio Calculations on the Photochemically Formed Dewar Isomers of the 4(3H)-Pyrimidinone Derivatives

1997 ◽  
Vol 62 (9) ◽  
pp. 2711-2719 ◽  
Author(s):  
Shun-ichi Hirokami ◽  
Akihiro Murao ◽  
Hiroko Kakuda ◽  
Hiroyuki Shinoda ◽  
Yoshinori Koga
Keyword(s):  
Ab Initio Calculations ◽  
Ab Initio ◽  
Crystal Structures ◽  
X Ray

scholarly journals Ab initio study of elastic anisotropies and thermal conductivities of rhenium diborides in different crystal structures

RSC Advances ◽  
2020 ◽  
Vol 10 (61) ◽  
pp. 37142-37152
Author(s):  
Yi X. Wang ◽  
Ying Y. Liu ◽  
Zheng X. Yan ◽  
W. Liu ◽  
Jian B. Gu
Keyword(s):  
Density Functional Theory ◽  
Ab Initio ◽  
Crystal Structures ◽  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Ab Initio Study ◽  
Ambient Conditions ◽  
Functional Theory ◽  
Thermal Conductivities

The phase stabilities, elastic anisotropies, and thermal conductivities of ReB2 diborides under ambient conditions have been investigated by using density functional theory calculations.

scholarly journals Ab initio computation for solid-state 31P NMR of inorganic phosphates: revisiting X-ray structures

2019 ◽  
Vol 21 (19) ◽  
pp. 10070-10074 ◽  
Author(s):  
Kartik Pilar ◽  
Zeyu Deng ◽  
Molleigh B. Preefer ◽  
Joya A. Cooley ◽  
Raphaële Clément ◽  
...  
Keyword(s):  
Solid State ◽  
Chemical Shift ◽  
Ab Initio ◽  
Crystal Structures ◽  
31P Nmr ◽  
Geometry Optimization ◽  
Chemical Shift Tensors ◽  
X Ray ◽  
Ab Initio Computation ◽  
Inorganic Phosphates

The complete 31P NMR chemical shift tensors for 22 inorganic phosphates obtained from ab initio computation are found to correspond closely to experimentally obtained parameters. The cases where correspondence is significantly improved upon geometry optimization point to the crystal structures requiring correction.

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