Internal coordinate mechanics

Internal Coordinate Mechanics

Submitted to:Sir InamUlHaq

Submitted by:Asma Gulzar

Roll no:3005

BS(hons)Chem 1st Semester

UNIVERSITY

OF EDUCATION

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UNIVERSITY OF EDUCATION,OKARA

CAMPUS

Table of Contents:

Introduction

Motivation OR Objectives

Importance& Scope

Comparison

Findings

Summary

Conclusion

References

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Introduction: ICM stands for Internal Coordinate

Mechanics and was first designed and built to predict low energy conformations of molecules by sampling the space of internal coordinates (bond lengths, bond angles and dihedral angles) defining molecular geometry. In ICM each molecule is constructed as a tree from an entry atom where each next atom is build iteratively from the preceding three atoms via three internal variables. The rings kept rigid or imposed via additional restraints.


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ICM also is a programming environment for various tasks in computational chemistry and computational structural biology, sequence analysis and rational drug design. The original goal was to develop algorithms for energy optimization of several biopolymers with respect to an arbitrary subset of internal coordinates such as bond lengths, bond angles torsion angles and phase angles. The efficient and general global optimization method which evolved from the original ICM method is still the central piece of the program. It is this basic algorithm which is used for peptide prediction, homology modeling and loop simulations, flexible macromolecular docking and energy refinement. However the complexity of problems related to structure prediction and analysis, as well as the desire for perfection, compactness and consistency, led to the program's expansion into neighboring areas such as graphics, chemistry, sequence analysis and database searches, mathematics, statistics and plotting.


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Motivation Or Objective: ICM stands for Internal Coordinate

Mechanics and was first designed and built to predict low energy conformations of molecules by sampling the space of internal coordinates (bond lengths, bond angles anddihedral angles) defining molecular geometry. In ICM each molecule is constructed as a tree from an entry atom where each next atom is build iteratively from the preceding three atoms via three internal variables. The rings kept rigid or imposed via additional restraints.


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Importance&Scope: ICMFF (as well as ECEPP/3 which we

use for comparison in loop simulations) is an internal coordinate force

field, that is, its intramolecular energy is a function of

torsional degrees of freedom (with certain exceptions).

The two force fields also use the same standard residue

geometry


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Scope: he algorithm automatically generates

the Internal Coordinate Force Field (ICFF), ... of molecular force field development and the scope of molecular structures ... been parameterized using extensive quantum mechanics (QM) calculations

Development of a new physics-based internal coordinate mechanics force field and its application to ... longer limited by scope or accuracy to the experimentally characterized molecules .


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Comparison: The average and median RMSD’s computed for 4–11

residue loops with ECEPP/3 and for 4–13 residue loops

with ICMFF are listed in Table V. We did not carry out

simulations with ECEPP/3 for the longest and the most

time-consuming 12 and 13 residue loops. ICMFF performs better for the entire (4–11 residue) range of loop

lengths with the average RMSD of more than 20% lower

than for the ECEPP/3 force field.

RMSDs obtained with the two force fields grow almost

linearly with loop length. Two small peaks in RMSD take

place for 9 and 11 residue loops and are more pronounced for ECEPP/3 than for ICMFF. A similar trend,

at least for the loops with less than 11 residues, can be

observed in the results of Jacobson et al.

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Because the 4–

11 residue loop sets used in this work are the same as

those considered by Jacobson et al.,


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Two small peaks in RMSD take

place for 9 and 11 residue loops and are more pronounced for ECEPP/3 than for ICMFF. A similar trend,

at least for the loops with less than 11 residues, can be

observed in the results of Jacobson et al.

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Because the 4–

11 residue loop sets used in this work are the same as

those considered by Jacobson et al.,

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it is reasonable to

suggest that the unexpectedly higher RMSD for 9 and 11

residue loops may be caused by some other feature of

the set. For example, insufficient filtering could lead to a

higher percentage of structures with lower experimental

accuracy of the loop region. Unusual ionization states of

the loop residues, or relatively close proximity of ligands

or ions and so forth could also influence the outcome o


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Findings: The results showed that the conformation of

arachidonic acid docked into the ICM-identified docking site has less energy than that docked into the manually defined docking site for pseudo wild type 8R-LOX. The mutation at I805 resulted in no docking pocket found near Fe atom. The energy of the arachidonic acid conformation docked into the manually defined docking site is higher in mutant 8R-LOX than in wild type 8R-LOX. The arachidonic acid conformations are not productive conformations.


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Suggestion: In this research, we applied a computational

method, Internal Coordinate Mechanics (ICM), to model the interactions between 8R-LOX and its substrate arachidonic acid. Docking arachidonic acid to 8R-LOX was performed. The most favoured docked ligandconformations were retained. We compared the results of our simulation with a proposed model and concluded that the binding pocket identified in this study agrees with the proposed model partially


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Summary: All-atom force fields represent a very important tool used for

theoretical studies of biomolecular systems. They are essential for

many areas of computational chemistry including the prediction of

protein structure and function, the study of protein–protein interactions, and the prediction of structure and binding affinities of

protein–ligand complexes. Although the large size of conformational space and the complexity of the energy landscapes make

protein structure prediction using all-atom force-fields prohibitive

for all but smallest proteins and peptides, all-atom force fields are

emerging as a major tool for the refinement of protein models

generated using comparative modeling methods.

Although modern comparative modeling methods are able to

produce models resembling closely the native conformation when

protein structures with reasonable percentage of sequence identity


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Conclusion: Modeling by homology is a sequential process of (i)

alignment of a query sequence with the template; (ii)

mapping regions which can deviate substantially

from the template; (iii) prediction of side chains, and

(iv) prediction of loops. An error at each step is

unrecoverable by later procedures, therefore early

steps have larger practical importance.

Prediction map building is important because it

precedes prediction of side chains and loops. Automated methods to predict the extent of local deviations around gaps and in the weak un-gapped parts

of the alignment should be developed. Structural

significance statistics based on the alignment score


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Reference: .wikipedia.org/wiki/Internal_Coordina

te_Mechanics(31.01.15)

wikipedia.org/wiki/Talk%3AInternal_C

oordinate_Mechanics

ablab.ucsd.edu/pdf/11_Development_

Arnautova_Proteins.pd

www.ncbi.nlm.nih.gov/pubmed/948549

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Education

Internal coordinate mechanics