New Media: A Double-Edged Sword in Support of Public Engagement with Science: A double-edged sword in support of public engagement with science

Ayelet Baram-Tsabari; Amit M. Schejter

doi:10.1007/978-3-030-14610-8_5

New Media: A Double-Edged Sword in Support of Public Engagement with Science: A double-edged sword in support of public engagement with science

Ayelet Baram-Tsabari, Amit M. Schejter

Technion - Israel Institute of Technology, Ben-Gurion University of the Negev

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

Abstract

Predicting the binding mode of flexible polypeptides to proteins is an important task that falls outside the domain of applicability of most small molecule and protein−protein docking tools. Here, we test the small molecule flexible ligand docking program Glide on a set of 19 non-$-helical peptides and systematically improve pose prediction accuracy by enhancing Glide sampling for flexible polypeptides. In addition, scoring of the poses was improved by post-processing with physics-based implicit solvent MM- GBSA calculations. Using the best RMSD among the top 10 scoring poses as a metric, the success rate (RMSD ≤ 2.0 Å for the interface backbone atoms) increased from 21% with default Glide SP settings to 58% with the enhanced peptide sampling and scoring protocol in the case of redocking to the native protein structure. This approaches the accuracy of the recently developed Rosetta FlexPepDock method (63% success for these 19 peptides) while being over 100 times faster. Cross-docking was performed for a subset of cases where an unbound receptor structure was available, and in that case, 40% of peptides were docked successfully. We analyze the results and find that the optimized polypeptide protocol is most accurate for extended peptides of limited size and number of formal charges, defining a domain of applicability for this approach.

Original language	Undefined/Unknown
Title of host publication	Learning In a Networked Society: Spontaneous and Designed Technology Enhanced Learning Communities
Subtitle of host publication	Spontaneous and Designed Technology Enhanced Learning Communities
Editors	Yael Kali, Ayelet Baram-Tsabari, Amit M. Schejter
Pages	79-95
Number of pages	17
ISBN (Electronic)	9783030146108
DOIs	https://doi.org/10.1007/978-3-030-14610-8_5
State	Published - 27 Apr 2019

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/978-3-030-14610-8_5

Cite this

Baram-Tsabari, A., & Schejter, A. M. (2019). New Media: A Double-Edged Sword in Support of Public Engagement with Science: A double-edged sword in support of public engagement with science. In Y. Kali, A. Baram-Tsabari, & A. M. Schejter (Eds.), Learning In a Networked Society: Spontaneous and Designed Technology Enhanced Learning Communities: Spontaneous and Designed Technology Enhanced Learning Communities (pp. 79-95) https://doi.org/10.1007/978-3-030-14610-8_5

Baram-Tsabari, Ayelet ; Schejter, Amit M. / New Media: A Double-Edged Sword in Support of Public Engagement with Science : A double-edged sword in support of public engagement with science. Learning In a Networked Society: Spontaneous and Designed Technology Enhanced Learning Communities: Spontaneous and Designed Technology Enhanced Learning Communities. editor / Yael Kali ; Ayelet Baram-Tsabari ; Amit M. Schejter. 2019. pp. 79-95

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abstract = "Predicting the binding mode of flexible polypeptides to proteins is an important task that falls outside the domain of applicability of most small molecule and protein−protein docking tools. Here, we test the small molecule flexible ligand docking program Glide on a set of 19 non-$-helical peptides and systematically improve pose prediction accuracy by enhancing Glide sampling for flexible polypeptides. In addition, scoring of the poses was improved by post-processing with physics-based implicit solvent MM- GBSA calculations. Using the best RMSD among the top 10 scoring poses as a metric, the success rate (RMSD ≤ 2.0 {\AA} for the interface backbone atoms) increased from 21% with default Glide SP settings to 58% with the enhanced peptide sampling and scoring protocol in the case of redocking to the native protein structure. This approaches the accuracy of the recently developed Rosetta FlexPepDock method (63% success for these 19 peptides) while being over 100 times faster. Cross-docking was performed for a subset of cases where an unbound receptor structure was available, and in that case, 40% of peptides were docked successfully. We analyze the results and find that the optimized polypeptide protocol is most accurate for extended peptides of limited size and number of formal charges, defining a domain of applicability for this approach.",

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Baram-Tsabari, A & Schejter, AM 2019, New Media: A Double-Edged Sword in Support of Public Engagement with Science: A double-edged sword in support of public engagement with science. in Y Kali, A Baram-Tsabari & AM Schejter (eds), Learning In a Networked Society: Spontaneous and Designed Technology Enhanced Learning Communities: Spontaneous and Designed Technology Enhanced Learning Communities. pp. 79-95. https://doi.org/10.1007/978-3-030-14610-8_5

New Media: A Double-Edged Sword in Support of Public Engagement with Science: A double-edged sword in support of public engagement with science. / Baram-Tsabari, Ayelet ; Schejter, Amit M.
Learning In a Networked Society: Spontaneous and Designed Technology Enhanced Learning Communities: Spontaneous and Designed Technology Enhanced Learning Communities. ed. / Yael Kali; Ayelet Baram-Tsabari; Amit M. Schejter. 2019. p. 79-95.

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

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N2 - Predicting the binding mode of flexible polypeptides to proteins is an important task that falls outside the domain of applicability of most small molecule and protein−protein docking tools. Here, we test the small molecule flexible ligand docking program Glide on a set of 19 non-$-helical peptides and systematically improve pose prediction accuracy by enhancing Glide sampling for flexible polypeptides. In addition, scoring of the poses was improved by post-processing with physics-based implicit solvent MM- GBSA calculations. Using the best RMSD among the top 10 scoring poses as a metric, the success rate (RMSD ≤ 2.0 Å for the interface backbone atoms) increased from 21% with default Glide SP settings to 58% with the enhanced peptide sampling and scoring protocol in the case of redocking to the native protein structure. This approaches the accuracy of the recently developed Rosetta FlexPepDock method (63% success for these 19 peptides) while being over 100 times faster. Cross-docking was performed for a subset of cases where an unbound receptor structure was available, and in that case, 40% of peptides were docked successfully. We analyze the results and find that the optimized polypeptide protocol is most accurate for extended peptides of limited size and number of formal charges, defining a domain of applicability for this approach.

AB - Predicting the binding mode of flexible polypeptides to proteins is an important task that falls outside the domain of applicability of most small molecule and protein−protein docking tools. Here, we test the small molecule flexible ligand docking program Glide on a set of 19 non-$-helical peptides and systematically improve pose prediction accuracy by enhancing Glide sampling for flexible polypeptides. In addition, scoring of the poses was improved by post-processing with physics-based implicit solvent MM- GBSA calculations. Using the best RMSD among the top 10 scoring poses as a metric, the success rate (RMSD ≤ 2.0 Å for the interface backbone atoms) increased from 21% with default Glide SP settings to 58% with the enhanced peptide sampling and scoring protocol in the case of redocking to the native protein structure. This approaches the accuracy of the recently developed Rosetta FlexPepDock method (63% success for these 19 peptides) while being over 100 times faster. Cross-docking was performed for a subset of cases where an unbound receptor structure was available, and in that case, 40% of peptides were docked successfully. We analyze the results and find that the optimized polypeptide protocol is most accurate for extended peptides of limited size and number of formal charges, defining a domain of applicability for this approach.

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Baram-Tsabari A , Schejter AM. New Media: A Double-Edged Sword in Support of Public Engagement with Science: A double-edged sword in support of public engagement with science. In Kali Y, Baram-Tsabari A, Schejter AM, editors, Learning In a Networked Society: Spontaneous and Designed Technology Enhanced Learning Communities: Spontaneous and Designed Technology Enhanced Learning Communities. 2019. p. 79-95 doi: 10.1007/978-3-030-14610-8_5