10.8 The Partition Function for Ensembles
487
behavior is preferred biologically, so that structure is preserved over a range of
temperatures below the melting point.
Observations of the helical fraction are possible using ultra-violet absorption
spectra. Experimental fits favor a cooperative model with ‘zipper’ behavior, i.e. the
helical transition occurs in one direction and completes once started. 55
Protein Design
The protein folding problem has an associated inverse problem: What sequences of
amino acids produce a reliable protein of given structure and function? Reliability
for proteins has several aspects:
• Energetic stability: Secondary and tertiary structure that are energetically favorable over competing alternative structures;
• Mutation insensitivity: A variety of single nucleotide mutations produce proteins
which retain functionality;
• Structural flexibility: Some alterations of amino acids in backbone and side
chains are allowed;
• Environmental durability: Structure should maintain integrity under natural
conditions and their expected variations.
• Reproduciblity: A shortened time needed to regenerate a protein adds to its
viability;
• Lockout resistivity: Protected and alternate structures with alternate functional
pathways (‘pathway redundancy’) adds resistivity to various biochemical or viral
degradations;
• Intergrationality: As the structure of the protein affects its position in the network
of functionalities in a cell, good de novo design must include ramifications on this
network.
Nature has found solutions to the design problem through the trial and error that
follows genetic code mutation. But with 20 amino acids, there are 20 100 > 10 126
possible proteins with just 100 amino acids in sequence. A human cell produces
perhaps 100,000 of these. There is a vast landscape of other possible de novo
proteins waiting exploration.
With computer programming, we are now near to having some answers to
protein design problems with computer time scales much smaller than evolution
has taken! 56
The designed proteins will have good application as
55 When comparing to experiment, the enthalpy change is usually taken as a fitting parameter, since,
in vivo, the change in enthalpy due to the desorption of water is difficult to calculate.
56 A functioning cell took a billion years of evolution. Future quantum computers together with
some organizing principles may make the analysis of even long amino acid chains tractable in
hours.
487
behavior is preferred biologically, so that structure is preserved over a range of
temperatures below the melting point.
Observations of the helical fraction are possible using ultra-violet absorption
spectra. Experimental fits favor a cooperative model with ‘zipper’ behavior, i.e. the
helical transition occurs in one direction and completes once started. 55
Protein Design
The protein folding problem has an associated inverse problem: What sequences of
amino acids produce a reliable protein of given structure and function? Reliability
for proteins has several aspects:
• Energetic stability: Secondary and tertiary structure that are energetically favorable over competing alternative structures;
• Mutation insensitivity: A variety of single nucleotide mutations produce proteins
which retain functionality;
• Structural flexibility: Some alterations of amino acids in backbone and side
chains are allowed;
• Environmental durability: Structure should maintain integrity under natural
conditions and their expected variations.
• Reproduciblity: A shortened time needed to regenerate a protein adds to its
viability;
• Lockout resistivity: Protected and alternate structures with alternate functional
pathways (‘pathway redundancy’) adds resistivity to various biochemical or viral
degradations;
• Intergrationality: As the structure of the protein affects its position in the network
of functionalities in a cell, good de novo design must include ramifications on this
network.
Nature has found solutions to the design problem through the trial and error that
follows genetic code mutation. But with 20 amino acids, there are 20 100 > 10 126
possible proteins with just 100 amino acids in sequence. A human cell produces
perhaps 100,000 of these. There is a vast landscape of other possible de novo
proteins waiting exploration.
With computer programming, we are now near to having some answers to
protein design problems with computer time scales much smaller than evolution
has taken! 56
The designed proteins will have good application as
55 When comparing to experiment, the enthalpy change is usually taken as a fitting parameter, since,
in vivo, the change in enthalpy due to the desorption of water is difficult to calculate.
56 A functioning cell took a billion years of evolution. Future quantum computers together with
some organizing principles may make the analysis of even long amino acid chains tractable in
hours.