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Incorporating molecular flexibility and conformational variability into crystal structure prediction

Incorporating molecular flexibility and conformational variability into crystal structure prediction
Incorporating molecular flexibility and conformational variability into crystal structure prediction

The ability to predict the properties of a crystal structure before any empirical analysis or laboratory work has commenced offers the opportunity for vast reductions in research and development costs for new products. This research focuses on a novel methodology to incorporate molecular flxibility into crystal structure prediction (CSP).

Chapter 3: The quantification of the effect of incorporating molecular flexibility and a revised Williams99 potential in the lattice energy minimisation finds that 5.5% and 6.3% more observed crystal structure matches, respectively, lie within 1kJ mol-1 of the calculated global energy minimum structure.

Chapter 4: A novel method is presented that simultaneously samples the molecularconformational space and the unit cell parameters when generating crystal structures where the former employs molecular principal displacements. This method was used for one test molecule that possesses 3 known polymorphs where only 1 is found when a standard CSP approach is used; this method now locates all 3 polymorphs.

Chapter 5: Presents a scientifically robust and computationally efficient method for finding a set of principal displacements and their corresponding contributions for converting one molecular conformation into another.

Chapter 6: The molecular strain energy induced by crystal packing forces was calculated for 224 molecules. It was found that a maximum number of principal displacements up to a force constant value of 0:084 mDyneA-1 were required to accurately reproduce the in-crystal conformation from its gas phase conformer for approximately 95% of cases.

Chapters 7 & 8: Present two CSP case studies. The first was a sixth blind test molecule that failed to be predicted when using a rigid molecule search procedure coupled with a flexible molecule lattice energy minimisation and hence was used as motivation to implement the methodology presented in Chapter 4 on the second case study of a novel herbicide molecule.

University of Southampton
Gee, Thomas Simon
e5c34f80-388e-4cb4-a705-5452c514291e
Gee, Thomas Simon
e5c34f80-388e-4cb4-a705-5452c514291e
Day, Graeme M.
e3be79ba-ad12-4461-b735-74d5c4355636

Gee, Thomas Simon (2017) Incorporating molecular flexibility and conformational variability into crystal structure prediction. University of Southampton, Doctoral Thesis, 276pp.

Record type: Thesis (Doctoral)

Abstract

The ability to predict the properties of a crystal structure before any empirical analysis or laboratory work has commenced offers the opportunity for vast reductions in research and development costs for new products. This research focuses on a novel methodology to incorporate molecular flxibility into crystal structure prediction (CSP).

Chapter 3: The quantification of the effect of incorporating molecular flexibility and a revised Williams99 potential in the lattice energy minimisation finds that 5.5% and 6.3% more observed crystal structure matches, respectively, lie within 1kJ mol-1 of the calculated global energy minimum structure.

Chapter 4: A novel method is presented that simultaneously samples the molecularconformational space and the unit cell parameters when generating crystal structures where the former employs molecular principal displacements. This method was used for one test molecule that possesses 3 known polymorphs where only 1 is found when a standard CSP approach is used; this method now locates all 3 polymorphs.

Chapter 5: Presents a scientifically robust and computationally efficient method for finding a set of principal displacements and their corresponding contributions for converting one molecular conformation into another.

Chapter 6: The molecular strain energy induced by crystal packing forces was calculated for 224 molecules. It was found that a maximum number of principal displacements up to a force constant value of 0:084 mDyneA-1 were required to accurately reproduce the in-crystal conformation from its gas phase conformer for approximately 95% of cases.

Chapters 7 & 8: Present two CSP case studies. The first was a sixth blind test molecule that failed to be predicted when using a rigid molecule search procedure coupled with a flexible molecule lattice energy minimisation and hence was used as motivation to implement the methodology presented in Chapter 4 on the second case study of a novel herbicide molecule.

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Published date: April 2017

Identifiers

Local EPrints ID: 414054
URI: http://eprints.soton.ac.uk/id/eprint/414054
PURE UUID: 431cd188-22c7-44e9-8377-06c8f091d32e
ORCID for Graeme M. Day: ORCID iD orcid.org/0000-0001-8396-2771

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Date deposited: 13 Sep 2017 16:31
Last modified: 29 Jun 2020 04:01

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Contributors

Author: Thomas Simon Gee
Thesis advisor: Graeme M. Day ORCID iD

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