Introduction GOLD software GOLD Genetic Optimisation for Ligand

Introduction- GOLD software • GOLD- Genetic Optimisation for Ligand Docking • Scoring Function- Goldscore： Fitness＝S(hb_ext)＋1. 375×S(vdw_ext)＋S(hb_int)＋S(bar) • van der Waals‘ forces → Lennard-Jones potential • Hydrogen bond →

Introduction- Genetic Algorithm START Encoding New Population Initial population Generation Crossover ased toward etter ‘fitters’! Selection N Termination ? Y STOP Mutation Evaluation Decoding Solutions Fitness Computation

Introduction- GOLD Default 1 2 times speed-up 3 times speed-up 7 -8 times speed-up Population Size 100 100 Selection Pressure 1. 1 100000 50000 30000 10000 No. of Islands 5 5 3 1 Niche Size 2 2 Migrate 10 10 10 0 95 95 95 100 100 populations each! No. of Operations operations Mutate Crossover A random pick: keep the frequency this ratio! Sset as 0 island becaus migrat betwe ‘island

Note • • • • • • Why some fitness function is higher than final score during docking ? Information on the Progress of Docking Runs … During a docking run, the fitness score may appear to get worse as the docking proceeds. This is due to the fact that the effects of poor H-bond geometry and close nonbonded contacts are artificially down-weighted at early stages of the docking (annealing). Only the final fitness score (i. e. from the completed docking) has any meaning. … Van der Waals and Hydrogen Bonding Annealing Parameters When Gold. Score is being used, the annealing parameters, Van der Waals and Hydrogen Bonding, allow poor hydrogen bonds to occur at the beginning of a genetic algorithm run, in the expectation that they will evolve to better solutions. (this is in more details now! Can read later!) The selection pressure is defined as the ratio between the probability that the most fit member of the population is selected as a parent to the probability that an average member is selected as a parent. Too high a selection pressure will result in the population converging too early. (Yes, higher this value, more biased to fitter chromosomes!) Niche size: 變化形 niches; 1. 壁龕 2. 合適的職務(或地位等)[(+in)] You can then find your own niche in public life. 那時候你就可以在社會上 找到適 合自己的 作了。 3. 利基 vt. 及物動詞 變化形 niches; 1. 把(雕像等)放入壁龕[H] (for keep diversity of conformations in a population!): Niching is a common technique used in genetic algorithms to preserve diversity within the population. In GOLD, two individuals share the same niche if the rmsd between the coordinates of their donor and acceptor atoms is less than 1. 0 Å . When adding a new individual to the population, a count is made of the number of individuals in the population that inhabit the same niche as the new chromosome. If there are more than Niche. Size individuals in the niche, then the new individual replaces the worst member of the niche rather than the worst member of the total population (don’t know when the replacement of individuals happens, but, knowing its meaning first! … typical value is 2)

In Autodock: • ga_elitism <integer> (usually is 1) • [1]This is used in the selection mechanism of the GA. This is the number of top individuals that are guaranteed to survive into the next generation. • Crossover and mutation are performed on random members of the population according to user-defined rates of crossover and mutation. First, crossover is performed. Two-point crossover is used, with breaks occurring only between genes, never within a gene—this prevents erratic changes in the real values of the genes. Thus, both parents’ chromosomes would be broken into three pieces at the same gene positions, each piece containing one or more genes; for instance, ABC and abc. The chromosomes of the resulting offspring after two point crossover would be Ab. C and a. Bc. These offspring replace the parents in the population, keeping the population size constant.