In my benchmarks, substr is about twice as fast as a /..../g regex for getting the next X characters:

cail:~/work/perl/monks$ cat 966488.pl 
#!/usr/bin/env perl
use Modern::Perl;
use Benchmark qw(:all);

my $string = '';
for (1..1_000_000){  # make a million-char string
    $string .= qw(A C G T)[rand(4)];
}
cmpthese( 100, {
    'regex'     => \&regex,
    'substring' => \&substring,
});

sub substring {
    my $str = $string;
    my %h;
    while(length($str) % 3){    # snip to 3-letter boundary
        substr($str,-1, 1, '');
    }
    while($_ = substr($str,0,3,'')){
        $h{$_}++;
    }
}

sub regex {
    my $str = $string;
    my %h;
    for ($str =~ /.../g){
        $h{$_}++;
    }
}
cail:~/work/perl/monks$ perl 966488.pl 
            Rate     regex substring
regex     5.78/s        --      -49%
substring 11.4/s       97%        --
[download]

Of course, if you only want to match certain letters, then you're back to a regex. But in that case, I might still try stripping out all the stuff I don't want with tr//, followed by substr to break it into pieces.