Computational design of cephradine synthase in a new scaffold identified from structural databases

2017 ◽  
Vol 53 (54) ◽  
pp. 7604-7607 ◽  
Author(s):  
Xiaoqiang Huang ◽  
Jing Xue ◽  
Yushan Zhu
Keyword(s):  
Computational Design ◽  
Protein Scaffold ◽  
Lactam Antibiotic ◽  
Structural Databases ◽  
New Protein

A new protein scaffold was identified and redesigned to catalyze the synthesis of β-lactam antibiotic cephradine.

Computational Design of New Protein Catalysts

2011 ◽  
pp. 241-266 ◽  
Author(s):  
Gert Kiss ◽  
Scott A. Johnson ◽  
Geoffrey Nosrati ◽  
Nihan Çelebi-Ölçüm ◽  
Seonah Kim ◽  
...  
Keyword(s):  
Computational Design ◽  
New Protein

scholarly journals Computational design of structured loops for new protein functions

2019 ◽  
Vol 400 (3) ◽  
pp. 275-288 ◽  
Author(s):  
Kale Kundert ◽  
Tanja Kortemme
Keyword(s):  
Protein Design ◽  
Protein Function ◽  
Structure Prediction ◽  
Computational Design ◽  
Loop Structure ◽  
Functional Sites ◽  
Loop Design ◽  
Routine Design ◽  
Protein Functions ◽  
New Protein

Abstract The ability to engineer the precise geometries, fine-tuned energetics and subtle dynamics that are characteristic of functional proteins is a major unsolved challenge in the field of computational protein design. In natural proteins, functional sites exhibiting these properties often feature structured loops. However, unlike the elements of secondary structures that comprise idealized protein folds, structured loops have been difficult to design computationally. Addressing this shortcoming in a general way is a necessary first step towards the routine design of protein function. In this perspective, we will describe the progress that has been made on this problem and discuss how recent advances in the field of loop structure prediction can be harnessed and applied to the inverse problem of computational loop design.

scholarly journals Computationally-guided tuning of ligand sensitivity in a GPCR-based sensor

2021 ◽  
Author(s):  
Daniel Keri ◽  
Reto B. Cola ◽  
Kagiampaki Zacharoula ◽  
Tommaso Patriarchi ◽  
Patrick Barth
Keyword(s):  
Computational Design ◽  
Fluorescent Sensors ◽  
Proof Of Concept ◽  
Molecular Tools ◽  
Transmembrane Region ◽  
Endogenous Ligands ◽  
Protein Scaffold ◽  
Sensor Sensitivity ◽  
Ligand Sensitivity

Genetically-encoded fluorescent sensors for neuromodulators are increasingly used molecular tools in neuroscience. However, these protein-based biosensors are often limited by the sensitivity of the protein scaffold towards endogenous ligands. Here, we explored the possibility of applying computational design approaches for enhancing sensor sensitivity. Using the dopamine sensor dLight1 as proof of concept, we designed two variants that boost the sensor's potency (EC50) for dopamine and norepinephrine by up to 5- and 15-fold, respectively. Interestingly, the largest effects were obtained through improved designed allosteric transmission in the transmembrane region of the sensor. Our approach should prove generally useful for enhancing sensing capabilities of a large variety of neuromodulator sensors.

scholarly journals Computational design of a modular protein sense-response system

Science ◽  
2019 ◽  
Vol 366 (6468) ◽  
pp. 1024-1028 ◽  
Author(s):  
Anum A. Glasgow ◽  
Yao-Ming Huang ◽  
Daniel J. Mandell ◽  
Michael Thompson ◽  
Ryan Ritterson ◽  
...  
Keyword(s):  
De Novo ◽  
Protein Structures ◽  
Computational Design ◽  
Metabolic Intermediate ◽  
Protein Interfaces ◽  
Substantial Progress ◽  
Valuable Compounds ◽  
Protein Sensors ◽  
New Protein

Sensing and responding to signals is a fundamental ability of living systems, but despite substantial progress in the computational design of new protein structures, there is no general approach for engineering arbitrary new protein sensors. Here, we describe a generalizable computational strategy for designing sensor-actuator proteins by building binding sites de novo into heterodimeric protein-protein interfaces and coupling ligand sensing to modular actuation through split reporters. Using this approach, we designed protein sensors that respond to farnesyl pyrophosphate, a metabolic intermediate in the production of valuable compounds. The sensors are functional in vitro and in cells, and the crystal structure of the engineered binding site closely matches the design model. Our computational design strategy opens broad avenues to link biological outputs to new signals.

scholarly journals Tracking Molecular Recognition at the Atomic Level with a New Protein Scaffold Based on the OB-Fold

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e86050 ◽  
Author(s):  
John D. Steemson ◽  
Matthias Baake ◽  
Jasna Rakonjac ◽  
Vickery L. Arcus ◽  
Mark T. Liddament
Keyword(s):  
Molecular Recognition ◽  
Atomic Level ◽  
Protein Scaffold ◽  
Ob Fold ◽  
New Protein

scholarly journals Computational design of a modular protein sense/response system

2019 ◽  
Author(s):  
Anum A. Glasgow ◽  
Yao-Ming Huang ◽  
Daniel J. Mandell ◽  
Michael Thompson ◽  
Ryan Ritterson ◽  
...  
Keyword(s):  
De Novo ◽  
Protein Structures ◽  
Computational Design ◽  
Metabolic Intermediate ◽  
Signaling Systems ◽  
Engineering Strategy ◽  
Valuable Compounds ◽  
Protein Sensors ◽  
New Protein

ABSTRACTSensing and responding to signals is a fundamental ability of living systems, but despite remarkable progress in computational design of new protein structures, there is no general approach for engineering arbitrary new protein sensors. Here we describe a generalizable computational strategy for designing sensor/actuator proteins by building binding sites de novo into heterodimeric protein-protein interfaces and coupling ligand sensing to modular actuation via split reporters. Using this approach, we designed protein sensors that respond to farnesyl pyrophosphate, a metabolic intermediate in the production of valuable compounds. The sensors are functional in vitro and in cells, and the crystal structure of the engineered binding site matches the design model with atomic accuracy. Our computational design strategy opens broad avenues to link biological outputs to new signals.One Sentence SummaryAn engineering strategy to design modular synthetic signaling systems that respond to new small molecule inputs.

Computational Design and Study of Artificial Selenoenzyme with Controllable Activity Based on an Allosteric Protein Scaffold

2019 ◽  
Vol 25 (44) ◽  
pp. 10350-10358
Author(s):  
Siyuan Li ◽  
Wanjia Xu ◽  
Shengnan Chu ◽  
Ningning Ma ◽  
Shengda Liu ◽  
...  
Keyword(s):  
Computational Design ◽  
Protein Scaffold ◽  
Allosteric Protein
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