{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/45091"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/45091","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Computer simulation of free energies to predict cis/trans equilibria of prolyl peptides and solvation free energies of phenylalanyl peptides","abstract":"Two computer simulation studies were performed; one to help understand the structure-function relationships of prolyl peptides (Part I) and the other to help predict more efficient pharmaceutical drug delivery by molecular modification of small peptides (Part II). In Part I, the free energy perturbation (FEP) method, using AMBER, was utilized to calculate the Gibbs free energy difference between <i>cis</i> and <i>trans</i> conformers of Ace-Tyr-Pro- NMe and Ace-Asn-Pro-NMe, from which the ratio of <i>cis</i> to <i>trans</i> conformers was obtained. Our simulation generated much lower <i>%cis</i> for both peptides as compared with experimental values and possible problems in our computational schemes are presented. However, our results were encouraging in that they predicted preference of <i>trans</i> conformers for both peptides and higher <i>%cis</i> for Ace-Tyr-Pro-NMe, compared to Ace-Asn-Pro-NMe, which agrees with experimental results. Part II applied semi empirical (AMS0L) and microscopic simulation (POLARIS) methods to obtain the solvation free energies of a series of phenylalanyl peptides with various degrees of methylation on their backbone nitrogens. It was clearly predicted that as a peptide length increased, so solvation free energy decreased, indicating less favorable permeability through the cell membrane system, in agreement with data in the literature. AMSOL also showed that solvation free energy change upon methylation was variable depending on the position of the substituted backbone nitrogen, which disagrees with the literature. However, non-systematic solvation free energy change of small amines upon methylation was successfully predicted by AMSOL, in good accord with experimental data.","abstract_html":"Two computer simulation studies were performed; one to help understand the structure-function relationships of prolyl peptides (Part I) and the other to help predict more efficient pharmaceutical drug delivery by molecular modification of small peptides (Part II). In Part I, the free energy perturbation (FEP) method, using AMBER, was utilized to calculate the Gibbs free energy difference between &lt;i&gt;cis&lt;/i&gt; and &lt;i&gt;trans&lt;/i&gt; conformers of Ace-Tyr-Pro- NMe and Ace-Asn-Pro-NMe, from which the ratio of &lt;i&gt;cis&lt;/i&gt; to &lt;i&gt;trans&lt;/i&gt; conformers was obtained. Our simulation generated much lower &lt;i&gt;%cis&lt;/i&gt; for both peptides as compared with experimental values and possible problems in our computational schemes are presented. However, our results were encouraging in that they predicted preference of &lt;i&gt;trans&lt;/i&gt; conformers for both peptides and higher &lt;i&gt;%cis&lt;/i&gt; for Ace-Tyr-Pro-NMe, compared to Ace-Asn-Pro-NMe, which agrees with experimental results. Part II applied semi empirical (AMS0L) and microscopic simulation (POLARIS) methods to obtain the solvation free energies of a series of phenylalanyl peptides with various degrees of methylation on their backbone nitrogens. It was clearly predicted that as a peptide length increased, so solvation free energy decreased, indicating less favorable permeability through the cell membrane system, in agreement with data in the literature. AMSOL also showed that solvation free energy change upon methylation was variable depending on the position of the substituted backbone nitrogen, which disagrees with the literature. However, non-systematic solvation free energy change of small amines upon methylation was successfully predicted by AMSOL, in good accord with experimental data.","abstract_has_math":false,"creators":["Kurusu, Tamaki"],"institution":"Virginia Tech","degree_name":"Master of Science","degree_level":"masters","degree_discipline":"Biochemistry","degree_department":"Biochemistry","school":null,"contributors":[],"advisors":[],"committee_chairs":["Bevan, David R."],"committee_members":["Newton, William E.","Gregory, Eugene M."],"year":1996,"date_issued":"1996-08-05","date_published":"1996-08-05","updated_at":"2026-07-22T22:18:41Z","subjects":["Molecular Modeling","Simulation","Free Energy","Proline","Solvation"],"languages":["en"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-10072005-094901"],"render_values":[{"text":"etd-10072005-094901","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10919/45091","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Bevan, David R."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Newton, William E.","Gregory, Eugene M."]},{"key":"dc:contributor.department","label":"Department","values":["Biochemistry"]},{"key":"dc:creator","label":"Author","values":["Kurusu, Tamaki"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2014-03-14T21:47:09Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2014-03-14T21:47:09Z","2005-10-07"]},{"key":"dc:date.issued","label":"Date","values":["1996-08-05"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.dcmitype","label":"Dc Type Dcmitype","values":["Text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Molecular Modeling","Simulation","Free Energy","Proline","Solvation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-10072005-094901"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10919/45091"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Two computer simulation studies were performed; one to help understand the structure-function relationships of prolyl peptides (Part I) and the other to help predict more efficient pharmaceutical drug delivery by molecular modification of small peptides (Part II). In Part I, the free energy perturbation (FEP) method, using AMBER, was utilized to calculate the Gibbs free energy difference between <i>cis</i> and <i>trans</i> conformers of Ace-Tyr-Pro- NMe and Ace-Asn-Pro-NMe, from which the ratio of <i>cis</i> to <i>trans</i> conformers was obtained. Our simulation generated much lower <i>%cis</i> for both peptides as compared with experimental values and possible problems in our computational schemes are presented. However, our results were encouraging in that they predicted preference of <i>trans</i> conformers for both peptides and higher <i>%cis</i> for Ace-Tyr-Pro-NMe, compared to Ace-Asn-Pro-NMe, which agrees with experimental results. Part II applied semi empirical (AMS0L) and microscopic simulation (POLARIS) methods to obtain the solvation free energies of a series of phenylalanyl peptides with various degrees of methylation on their backbone nitrogens. It was clearly predicted that as a peptide length increased, so solvation free energy decreased, indicating less favorable permeability through the cell membrane system, in agreement with data in the literature. AMSOL also showed that solvation free energy change upon methylation was variable depending on the position of the substituted backbone nitrogen, which disagrees with the literature. However, non-systematic solvation free energy change of small amines upon methylation was successfully predicted by AMSOL, in good accord with experimental data."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Master of Science"]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["BTD"]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Computer simulation of free energies to predict cis/trans equilibria of prolyl peptides and solvation free energies of phenylalanyl peptides"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Bevan, David R."],"dc:contributor.committeemember":["Newton, William E.","Gregory, Eugene M."],"dc:contributor.department":["Biochemistry"],"dc:creator":["Kurusu, Tamaki"],"dc:date.accessioned":["2014-03-14T21:47:09Z"],"dc:date.available":["2014-03-14T21:47:09Z","2005-10-07"],"dc:date.issued":["1996-08-05"],"dc:description.abstract":["Two computer simulation studies were performed; one to help understand the structure-function relationships of prolyl peptides (Part I) and the other to help predict more efficient pharmaceutical drug delivery by molecular modification of small peptides (Part II). In Part I, the free energy perturbation (FEP) method, using AMBER, was utilized to calculate the Gibbs free energy difference between <i>cis</i> and <i>trans</i> conformers of Ace-Tyr-Pro- NMe and Ace-Asn-Pro-NMe, from which the ratio of <i>cis</i> to <i>trans</i> conformers was obtained. Our simulation generated much lower <i>%cis</i> for both peptides as compared with experimental values and possible problems in our computational schemes are presented. However, our results were encouraging in that they predicted preference of <i>trans</i> conformers for both peptides and higher <i>%cis</i> for Ace-Tyr-Pro-NMe, compared to Ace-Asn-Pro-NMe, which agrees with experimental results. Part II applied semi empirical (AMS0L) and microscopic simulation (POLARIS) methods to obtain the solvation free energies of a series of phenylalanyl peptides with various degrees of methylation on their backbone nitrogens. It was clearly predicted that as a peptide length increased, so solvation free energy decreased, indicating less favorable permeability through the cell membrane system, in agreement with data in the literature. AMSOL also showed that solvation free energy change upon methylation was variable depending on the position of the substituted backbone nitrogen, which disagrees with the literature. However, non-systematic solvation free energy change of small amines upon methylation was successfully predicted by AMSOL, in good accord with experimental data."],"dc:description.degree":["Master of Science"],"dc:format.medium":["BTD"],"dc:format.mimetype":["application/pdf"],"dc:identifier.other":["etd-10072005-094901"],"dc:identifier.uri":["http://hdl.handle.net/10919/45091"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["Molecular Modeling","Simulation","Free Energy","Proline","Solvation"],"dc:title":["Computer simulation of free energies to predict cis/trans equilibria of prolyl peptides and solvation free energies of phenylalanyl peptides"],"dc:type":["Thesis"],"dc:type.dcmitype":["Text"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_level":["masters"],"thesis:degree_name":["Master of Science"],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:18:41Z"}