Translocon-associated biogenesis features and related methods, systems and products

1. A computer-based method to provide a protein sequence with a desired translocon-associated biogenesis feature, comprising:

i) establishing a desired translocon-associated biogenesis feature of a protein sequence, the desired translocon-associated biogenesis feature selected from a) desired protein topology, b) desired partitioning between protein integration and protein secretion and c) desired protein expression level;

ii) providing the protein or protein sequence with a set of translocon-associated biogenesis feature determinants;

iii) simulating, in a coordinate system with at least two spatial dimensions by a computer, one or more trajectories of the protein sequence with the set of translocon-associated biogenesis feature determinants, the one or more trajectories being simulation trajectories,

the one or more trajectories determining an translocon-associated biogenesis feature of the protein sequence with the translocon-associated biogenesis feature determinants,

wherein the simulating comprises projecting protein nascent chain dynamics onto a plane that intersects a translocon channel axis and bisects translocon lateral gate helices when the at least two spatial dimensions are two spatial dimensions, and the simulating comprises modeling the protein nascent chain dynamics in the at least two spatial dimensions when the at least two spatial dimensions are more than two spatial dimensions,

wherein the simulating operates in timesteps on the order of 100 nanoseconds over a span of 3 to 100 seconds;

iv) comparing the translocon-associated biogenesis feature of the protein sequence with the desired translocon-associated biogenesis feature of the protein sequence;

v) if the initial translocon-associated biogenesis feature of the protein sequence is different from the desired translocon-associated biogenesis feature of the protein sequence, modifying the set of translocon-associated biogenesis feature determinants, thus providing the protein sequence with a modified set of translocon-associated biogenesis feature determinants; and

vi) repeating steps iii)-v) with the modified set of translocon associated biogenesis feature determinants in place of the set of translocon associated biogenesis feature determinants, thereby modifying the one or more trajectories and resulting in a modified set of translocon associated biogenesis features, until the desired translocon-associated biogenesis feature is obtained, thus obtaining a set of translocon-associated biogenesis feature determinants suitable to be used for production of a protein or plasmid with the desired translocon-associated biogenesis feature.

2. The computer-based method of claim 1 , further comprising:

viii) producing a physical product including the protein with the desired translocon-associated biogenesis feature or polynucleotides encoding said protein.

3. The computer-based method of claim 2 , wherein the physical product is a synthesized protein or a synthesized plasmid.

4. The computer-based method of claim 1 , wherein the desired partitioning between protein integration and protein secretion comprises indication, for at least one segment of a trajectory, if the segment was secreted, retained or integrated, the protein topology represents, for at least one segment of the protein, if the segment has a type II topology, a type III topology or a different type of topology, and the expression level of the protein represents a percentage of the protein to be expressed according to a desired topology.

5. The computer-based method of claim 1 , wherein the modifying the set of translocon-associated biogenesis feature determinants comprises changing the sequence of the protein sequence.

6. The computer-based method of claim 5 , wherein changing the sequence of the protein sequence comprises one or more of: inserting, deleting or changing individual natural or artificial amino acids, segments of the protein sequence, replacing the protein sequence, and adding post translational modifications.

7. The computer-based method of claim 1 , wherein the set of translocon-associated biogenesis feature determinants suitable to be used for production of the protein sequence with the desired translocon-associated biogenesis feature consists of protein sequence-related translocon-associated biogenesis feature determinants.

8. The computer-based method of claim 1 , wherein the simulating one or more trajectories comprises:

i) simulating, by the computer, amino acids corresponding to the protein sequence and an associated translocon as a plurality of coarse grain particles;

ii) simulating, by the computer, confinement and driving force effects of an active protein inserter;

iii) simulating, by the computer, interactions between the coarse grain particles;

iv) calculating, by the computer, (a) evolution of a chain of the coarse grain particles corresponding to the protein sequence in the translocon at each of the timesteps, and (b) stochastic transitions between states of the coarse grain particles at each of the timesteps;

v) based on steps i)-iv), building, by the computer, the trajectories as translocon-associated protein trajectories; and

vi) providing, by the computer, a spatial representation of the trajectories.