Therefore, more experimentation must be performed to improve the current autonomous docking capabilities. Searching the conformational space for docking The search space in theory consists of all possible orientations and conformations of the protein paired with the ligand.
The success of a docking program depends on two components: One approach uses a matching technique that describes the protein and the ligand as complementary surfaces. Grid-based techniques, optimization methods, and increased computer speed have made docking simulation more realistic.
These are outlined below.
Docking approaches[ edit ] Two approaches are particularly popular within the molecular docking community. Download file opens in new window Development of a Guidance, Navigation and Control Architecture and Validation Process Enabling Autonomous Docking to a Tumbling Satellite The capability to routinely perform autonomous docking is a key enabling technology for future space exploration, as well as assembly and servicing missions for spacecraft and commercial satellites.
This protein structure and a Phd thesis on molecular docking of potential ligands serve as inputs to a docking program. A variety of conformational search strategies have been applied to the ligand and to the receptor.
These experiments led to the first autonomous docking with a tumbling target ever achieved in microgravity. Yet another approach is to use a Fourier shape descriptor technique.
Also, it more accurately models reality, whereas shape complimentary techniques are more of an abstraction. Particularly, in more challenging situations where the target spacecraft or satellite is tumbling, algorithms and strategies must be implemented to ensure the safety of both docking entities in the event of anomalies.
The obvious advantage of docking simulation is that ligand flexibility is easily incorporated, whereas shape complementarity techniques must use ingenious methods to incorporate flexibility in ligands.
Most docking programs in use account for the whole conformational space of the ligand flexible ligandand several attempt to model a flexible protein receptor.
Usually the structure has been determined using a biophysical technique such as x-ray crystallography or NMR spectroscopybut can also derive from homology modeling construction.
Mechanics of docking[ edit ] Docking flow-chart overview To perform a docking screen, the first requirement is a structure of the protein of interest.
Each "snapshot" of the pair is referred to as a pose. Each of these moves in the conformation space of the ligand induces a total energetic cost of the system.
The complementarity between the two surfaces amounts to the shape matching description that may help finding the complementary pose of docking the target and the ligand molecules. It aims to achieve an optimized conformation for both the protein and ligand and relative orientation between protein and ligand such that the free energy of the overall system is minimized.
Furthermore, the author also demonstrated successful docking in spite of the presence of measurement errors that were detected and rejected by an online fault detection algorithm.
However, in practice with current computational resources, it is impossible to exhaustively explore the search space—this would involve enumerating all possible distortions of each molecule molecules are dynamic and exist in an ensemble of conformational states and all possible rotational and translational orientations of the ligand relative to the protein at a given level of granularity.
They are also much more amenable to pharmacophore based approaches, since they use geometric descriptions of the ligands to find optimal binding. Simulation[ edit ] Simulating the docking process is much more complicated.
However, dificulties encountered in past docking missions conducted with expensive satellites on orbit have indicated a lack of maturity in the technologies required for such operations.
The results of these experiments will be discussed in this thesis. Another approach is to describe the hydrophobic features of the protein using turns in the main-chain atoms.
Clearly, simulation is computationally expensive, having to explore a large energy landscape.Murdock: A Molecular Docking Framework¶. Murdock is a Python package for the development and testing of automated molecular docking solutions. It has been developed as a convenient and efficient platform to implement new search algorithms, scoring functions, multi-step docking workflows and other features on a reliable platform, test them quickly and use the rich output to analyse advantages.
Applications and Improvements in the Molecular Modeling of Protein and Ligand Interactions Jason Bret Harris Harris, Jason Bret, "Applications and Improvements in the Molecular Modeling of Protein and Ligand Interactions.
" PhD diss., In this work, molecular docking and structural informatics have been integrated with other modeling. In the field of molecular modeling, docking is a method which predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex.
Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules using, for example, scoring functions. CHAPTER -5 MOLECULAR DOCKING STUDIES 5.
Molecular docking studies This chapter discusses about the molecular docking studies of the. boston university college of engineering dissertation accelerating molecular docking and binding site mapping using fpgas and gpus by bharat sukhwani.
Structural Prediction of Flexible Molecular Interactions THESIS SUBMITTED FOR THE DEGREE OF ^DOCTOR OF PHILOSOPHY" by with the flexibility of proteins poses a great challenge in the docking field. In this thesis we have encouraging me throughout my PhD studies.