Proteins design cycle

Fig. 26.2 The structure-based drug design cycle. The cycle can start either with a chemical lead, which is cocrystallized with the target protein, or with the structure of the target protein alone for de novo design. A number of cycles is usually necessary before one arrives at a suitable clinical candidate.

As protein design largely relies on educated guesswork, a successful project is likely going to be an iterative cycle of modeling, design, production of the sequence by genetic... 

In the absence of a quantitative theory of the effects of mutations on proteins, much less one for de novo design, intuitive design has much to speak for it. It is fast, resource efficient and in all likelihood as successful as any other method, if it is used carefully (see Section 3.2 for an example). Some of the prerequisites are access to a graphics workstation and the ability to visualize protein structure in three dimensions, access to various sequence and structure databases and tools for alignment and comparison. Its principles are simply stated using as much information as is available make the best guess you can about your novel sequence. Then express the protein and put it into the design cycle. 

For example, with the crystal structure of the aspartyl protease from human immundeficiency virus (HIV-1) in 1989 came the opportunity to design molecules to block this important enzyme that acts as a molecular scissors. HIV is the virus responsible for AIDS. Essential to viral replication, the HIV protease cuts long strands composed of many proteins into the functional proteins found in mature virus particles. This proteolysis occurs at the very end of the HIV replication cycle (Figure 7-1). The three-dimensional structural information derived from the x-ray crystal structure, combined with computer modeling techniques, allowed chemists to design potent, selective inhibitors of the protease enzyme (Figure... 

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